https://ijbms.mums.ac.ir/ Iranian Journal of Basic Medical Sciences en daily 1 Fri, 01 May 2026 00:00:00 +0330 Fri, 01 May 2026 00:00:00 +0330 https://ijbms.mums.ac.ir/article_27520.html Rosa damascena (Damask rose) has long been esteemed in traditional medicine for its neurocalming, anti-inflammatory, and antioxidant properties. Recent scientific interest highlights its potential to address exercise-induced physiological and psychological stress by modulating the neuroimmune axis. This narrative review synthesizes preclinical, clinical, and ethnobotanical evidence regarding R. damascena’s effects on neuroinflammation, oxidative stress, and post-exercise recovery. It aims to elucidate mechanistic pathways, assess translational applications, and propose evidence-based strategies for incorporation into sports medicine and athlete recovery protocols. A comprehensive literature search was conducted across biomedical databases up to May 2025. Eligible studies included in vitro, in vivo, and human research examining the physiological effects of R. damascena or its constituents in the context of neuropsychology, inflammation, oxidative damage, and exercise recovery. R. damascena exhibits multi-modal effects, including down-regulation of pro-inflammatory cytokines, attenuation of oxidative biomarkers, enhancement of parasympathetic activity, and modulation of serotonergic and GABAergic systems. Evidence supports its role in improving sleep quality, mood regulation, and cognitive function factors critical to athlete performance and resilience. Both preclinical and early-phase human studies indicate potential benefits in reducing delayed-onset muscle soreness (DOMS), accelerating recovery, and supporting autonomic balance. A translational framework is proposed to guide future applications and clinical trials. With its unique blend of neuroprotective, immunomodulatory, and adaptogenic properties, R. damascena presents a promising phytotherapeutic agent for exercise recovery. Bridging ancient medical traditions and modern sports science, it warrants further interdisciplinary investigation to validate its efficacy, determine optimal formulations, and ensure safety in diverse athletic populations. https://ijbms.mums.ac.ir/article_27615.html Triple-negative breast cancer (TNBC) is defined by profound heterogeneity, dormant metastatic reservoirs, and rapid therapy resistance. Building on our AI-Driven CRISPR Strategies in Breast Cancer framework, CRISPR–Cas9 is emerging as more than a gene-editing tool, capable of restoring circadian integrity, eliminating dormant clones, and re-programming immune surveillance. A structured PubMed, Scopus, and ClinicalTrials.gov review through 2025 integrated mechanistic, preclinical, and early clinical evidence. Beyond standard knockout, base, and prime editing, we highlight chrono-genomic repair of BMAL1/PER2, dormancy-focused synthetic-lethality screens, and genomic-collapse tactics for BRCA1-deficient tumors. Adaptive AI pipelines that iteratively refine guide RNAs and exosome-mimetic carriers, incorporating Boolean logic gates, were also evaluated for self-regulated, tumor-specific delivery. Proof-of-concept studies show that HER2 deletion, TP53 rescue, and ABCB1 silencing enhance chemosensitivity across luminal, HER2-positive, and TNBC models. Circadian restoration expands therapeutic windows and delays relapse in xenografts. Dormancy-directed CRISPR screens reveal unique vulnerabilities in disseminated tumor cells, whereas genomic collapse selectively destroys BRCA1-mutant clones. Integration with CAR-T cells and antibody–drug conjugates amplifies cytotoxicity, and transient nanoparticle or exosome systems improve solid-tumor penetration while minimizing off-target events. CRISPR–Cas9 is transitioning from a molecular scalpel to an adaptive, self-learning therapeutic ecosystem. By uniting AI-guided design, circadian reprogramming, dormancy eradication, and logic-gated delivery, the strategies detailed here define a next-generation precision-oncology paradigm capable of anticipating tumor evolution, overcoming resistance, and preventing metastatic relapse. https://ijbms.mums.ac.ir/article_27515.html Cystic echinococcosis (CE) is a neglected parasitic disease. Although several therapeutic approaches are available for CE, including PAIR (Puncture, Aspiration, Injection, Re-aspiration), surgery, chemotherapy with anthelmintic drugs, and waiting for inactive cysts, these methods face challenges, and treatment choices remain debated. Regarding chemotherapy, especially with albendazole (ABZ) as the first-line drug, efficacy is limited by poor solubility and low bioavailability. Recently, nanoparticle (NP)-based systems, or nanocarriers, have attracted much interest in drug delivery, with ABZ as the main focus. This review summarizes the latest progress in developing diverse nanocarrier systems, such as liposomes, polymeric NPs (PNPs), and metallic NPs, highlighting their potential for scolicidal activity and for improving therapeutic approaches for CE. In addition, diagnostic methods, including imaging techniques and serological tests, as well as emerging nanotechnology-based approaches such as biosensors and nanosensors, are briefly discussed to provide a more comprehensive perspective on CE management. Subsequently, the prospects and challenges of drug-loaded nanocarriers for the treatment of CE are briefly discussed to further encourage their use as a means to improve drug delivery performance in CE therapy.  https://ijbms.mums.ac.ir/article_27650.html Objective(s): This study aimed to assess the protective role of hesperidin (HSP), a citrus flavonoid, against di-(2-ethylhexyl) phthalate (DEHP)-induced kidney toxicity in rats, focusing on oxidative stress, apoptosis, inflammation, and anti-oxidant defense pathways.Materials and Methods: Thirty-five male rats were randomly assigned into five groups (7 per group):  control group, DEHP-treated group (1 g/kg), DEHP + HSP (100 mg/kg) group, DEHP + HSP (200 mg/kg) group, and HSP-alone group, and treated orally for 10 consecutive days.  Kidney tissues were collected for biochemical assays, including malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Gene expression of Nrf2, Keap1, HO-1, Bax, Bcl-2, Caspase-3, TLR-4, and NF-κB was analyzed using real-time PCR, and protein levels were evaluated using Western blotting.Results: DEHP significantly increased oxidative damage and the expression of inflammatory and apoptotic markers, while decreasing anti-oxidant parameters. Co-treatment with HSP, particularly at 200 mg/kg, restored anti-oxidant balance, reduced lipid peroxidation, and down-regulated the expression of TLR-4, NF-κB, and Caspase-3. Moreover, HSP increased Bcl-2 levels and enhanced Nrf2/HO-1 signaling, as confirmed by both gene and protein expression data.Conclusion: HSP demonstrates dose-dependent renoprotective effects against DEHP-induced nephrotoxicity in rats. The protective mechanism involves anti-oxidant enhancement and inhibition of oxidative stress-induced inflammation and apoptosis, supporting the therapeutic potential of HSP in managing phthalate-related renal injury. https://ijbms.mums.ac.ir/article_27572.html Kurarinone (KRN) is a major prenylated flavanone isolated from Sophora flavescens, widely recognized for its diverse pharmacological activities and growing therapeutic relevance. This review provides a comprehensive and updated overview of KRN, encompassing its botanical occurrence, phytochemical characteristics, structural elucidation, and biotransformation pathways, alongside in-depth analyses of its pharmacological activities, molecular mechanisms, and pharmacokinetic behavior across experimental models. A structured literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar using the keywords “Kurarinone,” “Sophora flavescens flavonoids,” “prenylated flavanones,” and related terms. Studies reporting natural occurrence, chemical isolation, biotransformation, physicochemical properties, pharmacological mechanisms, pharmacokinetics, and toxicity were included. In vitro and in vivo experimental studies and clinical disease models were prioritized, while non-primary sources and incomplete reports were excluded. KRN exhibited a broad pharmacological profile, including anticancer, anti-inflammatory, antibacterial, antiviral, and organ-protective effects, driven by its capacity to orchestrate multiple signaling networks. Mechanistically, KRN regulated pivotal molecular pathways, such as NF-κB, MAPK, JAK2/STAT3, PI3K/Akt, Nrf2/HO-1, and caspase-dependent apoptosis, thereby modulating inflammatory responses, oxidative stress, and cell apoptosis. Biotransformation studies reveal rapid conversion into glucuronide and hydroxyl conjugates. pharmacokinetic evidence indicated poor oral bioavailability (less than 50%), extensive Phase II metabolism, and tissue-specific accumulation, particularly in hepatic compartments. While these characteristics may contribute to therapeutic action, dose-dependent hepatotoxicity has been reported, highlighting critical translational challenges and the need for formulation advances and safety optimization. Future research should emphasize pharmacokinetic-pharmacodynamic modeling, nano-delivery systems, toxicity profiling, and well-designed clinical studies to support its translational development. https://ijbms.mums.ac.ir/article_27663.html Nanomedicine has transformed therapeutic strategies by enabling precise delivery of nucleic acid-based drugs, including small interfering RNA (siRNA), messenger RNA (mRNA), and antisense oligonucleotides. A landmark achievement is Onpattro (patisiran), the first FDA-approved RNAi therapy, which employs lipid nanoparticles (LNPs) to silence transthyretin in hereditary amyloidosis. Its approval validates RNAi as a viable therapeutic modality and underscores the central role of nanocarriers in clinical translation. Despite this success, barriers such as nanoparticle stability, targeted delivery, immunogenicity, and manufacturing scalability remain. Recent advances in mRNA vaccines, CRISPR-based gene editing, and stimuli-responsive nanoparticles are addressing these challenges, supported by growing clinical case studies and real-world data. This review highlights Onpattro’s clinical development, compares delivery platforms, discusses translational challenges, and examines emerging technologies that will guide the next generation of RNAi nanomedicines in personalized therapy. https://ijbms.mums.ac.ir/article_27577.html Non-small cell lung cancer (NSCLC) remains one of the leading causes of global cancer mortality despite advances in immunotherapy. While immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have transformed clinical outcomes for selected patients, response rates remain highly variable due to tumor heterogeneity, immune escape mechanisms, and evolving biomarker complexity. The need for dynamic, integrative biomarkers that better predict treatment response and guide personalized therapy is increasingly critical. This narrative review synthesizes recent advances (2023–2025) in genomic, transcriptomic, proteomic, metabolomic, and liquid-biopsy-based biomarkers relevant to NSCLC immunotherapy. Key databases, including PubMed, Scopus, and Web of Science, were screened, with emphasis on emerging artificial intelligence (AI) and digital twin–based frameworks supporting precision immuno-oncology. Across studies, single biomarkers such as PD-L1 or tumor mutational burden (TMB) demonstrate limited standalone predictive value. Multi-omic signatures incorporating circulating tumor DNA (ctDNA) fragmentomics, exosomal PD-L1, T-cell receptor (TCR) repertoire diversity, DDR alterations, metabolic checkpoint activity, and spatial immune profiling demonstrate improved accuracy and clinical relevance (clinical and preclinical evidence). AI-based multimodal models and digital immune twins further enhance predictive capacity by mapping resistance trajectories and simulating individualized therapeutic responses (computational/model-based evidence).The transition from static biomarkers toward integrated multi-omic and AI-driven decision frameworks represents a paradigm shift in NSCLC immunotherapy. These emerging platforms support a future of adaptive, anticipatory, and personalized treatment strategies with strong translational potential. https://ijbms.mums.ac.ir/article_27637.html MicroRNAs are non-coding small RNA molecules that play a significant role in regulating gene expression. Increasing lines of evidence have highlighted the microRNA dysregulation and neuroinflammation-associated apoptosis in common brain diseases, including Parkinson’s disease, Alzheimer’s disease, epilepsy, traumatic brain injury, depression, and migraine. In fact, microRNAs regulate multiple physiological and pathological processes, thus implicating them in both health and disease. Though studies have suggested that the alterations or modifications in microRNA-associated regulatory pathways might contribute to the disease pathogenesis, the underlying molecular mechanisms and the targeted genes remain exclusively unknown. We hope that the idea of using microRNAs as therapeutic targets for brain disorders is not far from reality, but important issues must be addressed before moving into clinical practice. The aim of this review is to enlighten the molecular mechanisms and targeted genes of microRNA implicated in the multifaceted brain disorders. Moreover, several microRNAs have been reported to be up-regulated following disease, but their targeted pathways have not been elucidated yet. This review also highlighted microRNAs that are expected to warrant further exploration of their mechanism of action. This comprehensive overview of the prediction of microRNAs’ functions might be helpful in providing more efficient insight for the development of microRNA-based therapeutic interventions for neuropsychiatric and neurodegenerative diseases. https://ijbms.mums.ac.ir/article_27600.html Objective(s): Acute kidney injury (AKI) is a severe, life-threatening complication of sepsis that often leads to renal failure. Thymoquinone, the main bioactive component of Nigella sativa, exhibits potent antioxidant and anti-inflammatory effects, protecting heart, liver, and kidney tissues in experimental studies. This study aimed to investigate the protective effects of thymoquinone on lipopolysaccharide (LPS)-induced AKI in mice by assessing oxidative stress, inflammatory mediators, pyroptosis factors, and renal function markers via modulation of oxidative stress and pyroptosis pathways.Materials and Methods: Thirty-two male C57BL/6 mice (20–25 g) were randomized into four groups: control, LPS, and two LPS groups treated with thymoquinone solubilized in Cremophor (1 or 10 mg/kg). AKI was induced by intraperitoneal injection of LPS (10 mg/kg). After 24 hr, blood samples were collected for blood urea nitrogen (BUN), cystatin C, and serum creatinine assays. Kidney homogenates were analyzed for malondialdehyde (MDA), superoxide dismutase (SOD), nitrite, interleukin-6 (IL-6), nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3), and caspase-1 levels.Results: Thymoquinone (10 mg/kg; PO) significantly decreased BUN (P<0.05), cystatin C (P<0.05), and serum creatinine (P<0.05) levels. It also reduced MDA concentration (P<0.05) and increased SOD activity (P<0.05), while nitrite levels remained unchanged. Furthermore, IL-6, NLRP3, and caspase-1 were significantly lower (for all factors, P<0.05) in thymoquinone-treated mice compared to the LPS group.Conclusion: Thymoquinone effectively attenuates LPS-induced AKI, likely by reducing oxidative stress, inhibiting pyroptosis and inflammation, and enhancing antioxidant defenses. https://ijbms.mums.ac.ir/article_27649.html Objective(s): Oral squamous cell carcinoma (OSCC) remains highly lethal and is driven, in part, by chronic NF-κB-mediated inflammation. Sorafenib, a multikinase inhibitor of RAF/VEGFR/PDGFR, can suppress these pathways, but its clinical utility is limited by hydrophobicity, toxicity, and poor tumor penetration. We engineered hyaluronic acid-coated niosomes encapsulating sorafenib (SOR@Nio/HA) to enable CD44-targeted delivery to OSCC cells.Materials and Methods: SOR@Nio/HA displayed a mean hydrodynamic diameter of 177±8 nm (PDI=0.23-0.26) and high encapsulation efficiency (86.34%), with pH-responsive release (45% at pH=5.5 and 30% at pH=7.4, in 24 hr).Results: In CAL27 cells, SOR@Nio/HA significantly enhanced cytotoxicity versus free sorafenib, lowering IC50 from 11.8±1.1 µM to 5.2±0.9 µM (P<0.01), and increased Annexin V/PI-defined apoptosis relative to controls. qRT-PCR showed suppression of NF-κB targets, with COX-2 and MMP-9 reduced to 0.35-fold and 0.32-fold of the control, respectively, alongside a pro-apoptotic shift in the BAX/BCL-2 axis.Conclusion: Collectively, these data indicate that SOR@Nio/HA improves intracellular delivery and potentiates sorafenib’s antitumor activity by CD44-mediated uptake and inhibition of NF-κB-driven inflammatory and invasive programs. HA-guided niosomal sorafenib warrants in vivo validation as a selective nanotherapeutic strategy for OSCC. https://ijbms.mums.ac.ir/article_27579.html Objective(s): This study aimed to investigate the protective effect and underlying mechanism of chrysophanol (CPH) on senile osteoporosis (OP) in rats. Materials and Methods: Twenty-four-month-old rats were divided into an aged OP model group and low- (10 mg/kg), medium- (20 mg/kg), and high-dose (50 mg/kg) CPH groups, with eight-month-old rats used as the control group. After 60 days of oral CPH administration, the bone mineral density (BMD), bone volume fraction (BV/TV), trabecular number (TbN), and trabecular separation (TbSp) of the femur were analysed using Micro-CT. Serum levels of bone formation markers (alkaline phosphatase, ALP; osteocalcin, OC) and bone resorption markers (type I collagen crosslinked N-telopeptide, NTX; tartrate-resistant acid phosphatase, TRACP) were determined by ELISA. Pathological changes in the femur were observed via H&E staining, and the expression of p-AKT and p-mTOR proteins in bone marrow was detected by western blotting.Results: Compared with those in the control group, the bone formation marker levels, BMD, BV/TV, and TbN in the model group significantly decreased, whereas the bone resorption marker levels, TbSp, and expression levels of p-AKT and p-mTOR significantly increased, with obvious bone structure destruction. CPH treatment reversed these changes in a dose dependent manner, significantly enhanced bone formation, inhibited bone resorption, improved bone density and microstructure, and down-regulated the expression of p-AKT and p-mTOR. Conclusion: CPH can effectively improve bone density and microstructure in aged osteoporotic rats, and its bone-protective effect may be related to the inhibition of the PI3K/AKT/mTOR signaling pathway. https://ijbms.mums.ac.ir/article_27661.html Objective(s): Research on the male gonadotoxic effects of olanzapine (OLZ) and the potential protective role of vitamin E (Vit E) remains limited. This investigation aimed to assess the toxic impact of OLZ on the testes integrity and the protective role of dietary Vit E. Materials and Methods: In this experimental study, twenty-eight rats were divided into four groups: a control group, a group administered 5 mg/kg of OLZ orally, a group receiving both OLZ and 100 mg/kg of Vit E, and a group treated with Vit E alone. We assessed testes dimensions, structural alterations, serum concentrations of testosterone and prolactin, sperm parameters, oxidative stress, and apoptosis. Additionally, the expression levels of microRNA (miR)-122 and miR-202-5p were quantified.Results: Administration of OLZ resulted in significant structural damages to the testes characterized by apoptosis, cellular stress, and disruption of miR-122 and miR-202-5p expression. Otherwise, Vit E restores the histological structure, apoptosis, and sperm quality affected by OLZ. Notably, hormonal profiles and indices of cellular stress showed significant improvement in rats receiving a combination of Vit E and OLZ. Furthermore, the expressions of miR-122 and miR-202-5p were normalized in the OLZ + Vit E treated group. Conclusion: This study highlights the protective role of dietary Vit E against OLZ-induced testicular toxicity by enhancing testicular histo-architecture, reducing stress markers, and modulating of microRNA expressions. https://ijbms.mums.ac.ir/article_27606.html Objective(s): This study investigated the mechanism by which quercetin suppresses oxidative stress and improves fibrosis in human pleural mesothelial cells (HPMCs) induced by the Mycobacterium tuberculosis-specific antigen early secretory antigen target protein-6 (ESAT-6) by activating the Nrf2/HO-1 signaling pathway, thereby suppressing oxidative stress.Materials and Methods: An in vitro model of ESAT-6-induced HPMC fibrosis was established. The effects of various concentrations of quercetin on HPMCs were assessed using the CCK-8 assay. Markers of oxidative stress, such as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH), were assessed. Immunofluorescence was utilized to detect levels of nuclear factor erythroid 2-related factor 2 (Nrf2), and western blot analysis was conducted to evaluate the protein levels of Nrf2, heme oxygenase-1 (HO-1), E-cadherin (E-cad), and α-smooth muscle actin (α-SMA).Results: Quercetin significantly improved ESAT-6-induced HPMC proliferation, reduced the oxidative stress marker MDA, and decreased the fibrosis marker α-SMA levels. It also promoted the translocation of Nrf2 into the nucleus in ESAT-6-induced pleural mesothelial cell fibrosis. Furthermore, quercetin enhanced the enzymatic activity of antioxidants, particularly GSH and SOD, and increased the expression levels of HO-1, Nrf2, and E-cad.Conclusion: The findings indicate that quercetin can inhibit oxidative stress by modulating the Nrf2 pathway and up-regulating HO-1 activity, thereby improving ESAT-6-induced pleural mesothelial cell fibrosis. https://ijbms.mums.ac.ir/article_27662.html Objective(s): Cirrhosis causes chronotropic dysfunction by weakening the β-adrenergic receptor (β-AR) signaling pathway in cirrhotic cardiomyopathy (CCM). Downstream signaling of glucocorticoids and dopamine receptors influences the β-AR pathway. Thus, the effects of glucocorticoids on chronotropic incompetence and the possible involved pathways were investigated in this experiment. Materials and Methods: Bile duct ligation (BDL) surgery was performed on Wistar rats to induce cirrhosis. Four weeks after BDL or sham surgery, the subjects were given an intramuscular injection of either saline (NS) or dexamethasone (dexa)  (2.2 mg/kg/day) for three consecutive days. In vivo, chronotropic responsiveness to isoproterenol and QTc interval were evaluated by electrocardiogram (ECG). Real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were performed to determine the effectiveness of dexa on dopamine D1, D2 receptors, and GNAL mRNA expression. Moreover, the tumor necrosis factor-alpha (TNF-α) and interleukin‐1beta (IL-1β) levels in rats’ hearts were assessed.Results: Dexa treatment reduced the prolonged QT intervals in cirrhosis. It also dedcreasd spleen weight, as well as TNF-α levels, which are increased in cirrhosis. Moreover, dexa increased D1 protein expression in IHC. Conclusion: Dexa effectively improved cirrotic heart by improving QT intervales and increasing spleen weight,  reducing a pro-inflammatory cytokine, and up-regulateing  D1 receptor protein expression.  https://ijbms.mums.ac.ir/article_27476.html Objective(s): Arginine-rich peptides have attracted interest because of their ability to interact with negatively charged cancer cell membranes. The present study aimed to evaluate the anticancer properties of a novel antimicrobial arginine-rich decapeptide (RL10) in vitro and in vivo. Materials and Methods: Cytotoxicity was assessed in breast (4T1), colon (SW480), and normal fibroblast (NIH3T3) cell lines by MTT assay following 48- and 72-hr treatment (6-400 µg/ml). Membrane integrity was examined in 4T1 cells after 48 hr using lactate dehydrogenase (LDH) release. Flow cytometry was applied to determine apoptosis induction and alterations in cell cycle distribution. Caspase 3/7 activity was also evaluated. Apoptosis-related gene expressions were analyzed using RT-PCR. The antitumor effect of RL10 was assessed in a murine 4T1 model, followed by histopathological analysis using H&E staining.Results: RL10 significantly declined cancer cell viability in a dose-dependent manner, with no toxicity on normal cells. No increase in LDH release was detected. Flow cytometry revealed 28.9% apoptosis induction and cell cycle arrest at the S and G2/M phases. Marked upregulation of the Casp9 gene suggested possible activation of the intrinsic apoptotic pathway; however, Bax, Bcl2, p53, and Casp8 expressions remained unchanged. In vivo, two weeks’ treatment with the peptide suppressed tumor growth by nearly 39% (P˂0.01), accompanied by increased apoptotic figures and reduced mitotic counts. Conclusion: These findings provide the first evidence that an arginine-rich short peptide exhibits anticancer activity through apoptosis induction and tumor growth inhibition, underscoring its potential as a candidate for cancer therapy or drug delivery systems. https://ijbms.mums.ac.ir/article_27574.html Objective(s): Chronic inflammatory pain significantly affects patient quality of life; however, existing treatment methods have limitations. Propolis is rich in various bioactive ingredients, such as flavonoids and phenolic acids. This study aimed to explore the effects and action mechanisms of propolis against chronic inflammatory pain.Materials and Methods: A mouse model of chronic inflammatory pain was established using Complete Freund’s adjuvant, with the mice divided into normal control, model, and propolis-treated groups. Body weight, pain score, foot volume, thermal pain threshold, mechanical pain threshold, and pathological changes in the toe tissue were recorded before injection (day 0) and on days 1, 7, 14, 21, and 28 after injection.After the experiment, changes in inflammatory factors (TNF-α, IL-4, IL-6, and IL-10) were detected, and the expression and distribution of proteins associated with the PKC-TRPV1-SP signalling axis in the toe, spinal cord, and hippocampus were detected by Western blot and immunofluorescence.Results: Propolis treatment significantly inhibited foot swelling, alleviated tissue inflammatory lesions, relieved pain, and increased heat and mechanical pain thresholds in mice. In addition, propolis inhibited the secretion of pro-inflammatory cytokines TNF-α, IL-4, and IL-6, promoted the secretion of the anti-inflammatory cytokine IL-10, and inhibited the expression of proteins related to the PKC-TRPV1-SP signalling axis.Conclusion: This study demonstrated that propolis exerts anti-inflammatory and analgesic effects by regulating the PKC-TRPV1-SP signalling axis. The findings offer new perspectives for the clinical treatment of chronic inflammatory pain and provide a reference for the development of new medications. https://ijbms.mums.ac.ir/article_27519.html Objective(s): Liver fibrosis can progress to hepatic encephalopathy (HE). While sorafenib is a drug employed to treat liver fibrosis, its use is linked to drug resistance and adverse effects. We examined the potential benefits of combining sorafenib with the probiotic Lactobacillus rhamnosus GG (LGG) on liver fibrosis and HE in bile duct ligated (BDL) rats. Materials and Methods: Forty male rats were randomly assigned to five groups of eight rats each, including sham, BDL, BDL+probiotic (LGG, 1×109 CFU/ml/day), BDL+sorafenib (20 mg/kg), and BDL+probiotic+sorafenib. First, rats receive probiotic LGG or solvent for 2 weeks. Following a one-week post-BDL recovery period, the animals received sorafenib and probiotic LGG for three consecutive weeks. Next, various parameters were appraised. Results: The combination of sorafenib with LGG led to less liver fibrosis when compared with sorafenib alone. This combination therapy also alleviated inflammation and oxidative species present in the liver and frontal cortex. Further, this combination diminished hepatic Toll-like receptor 4/ Nuclear factor kappa-β expression. Finally, it led to improved cognitive function in behavioral assessments compared to using sorafenib alone. Conclusion: Overall, combining a low dose of sorafenib with probiotic LGG may offer significant benefits for treating liver fibrosis and HE. https://ijbms.mums.ac.ir/article_27571.html Objective(s): Lung ischemia-reperfusion (IR) injury is a critical clinical condition characterized by oxidative stress, inflammation, and necroptosis, often leading to severe complications. Cannabidiol (CBD), a non-psychoactive cannabinoid, has demonstrated anti-oxidant and anti-inflammatory properties, but its role in modulating lung IR injury remains incompletely understood. This study investigated the protective effects of CBD on lung IR injury in rats, focusing on the RIPK1/RIPK3 necroptosis pathway and the HIF-1α/VEGF/eNOS signaling axis.Materials and Methods: Forty male Wistar albino rats were randomized into four groups: control, IR, IR+CBD (5 mg/kg), and CBD-only. Histopathological, immunohistochemical (TNF-α, Caspase-3), biochemical (TOS, TAS, OSI), and gene expression (RIPK1, RIPK3, HIF-1α, VEGF, eNOS) analyses were performed. The IR group exhibited significant oxidative stress, inflammation, and tissue damage, with elevated TNF-α, Caspase-3, TOS, OSI, and necroptosis/apoptosis markers.Results: CBD treatment markedly attenuated these effects, reducing oxidative stress (↑TAS, ↓TOS/OSI), suppressing inflammation (↓TNF-α), and inhibiting both apoptotic (↓Caspase-3) and necroptotic (↓RIPK1/RIPK3) pathways. Additionally, CBD down-regulated HIF-1α/VEGF/eNOS expression, suggesting modulation of hypoxia-responsive signaling. Conclusion: These findings demonstrate that CBD mitigates lung IR injury by targeting oxidative stress, inflammation, and cell death mechanisms, highlighting its potential as a therapeutic agent. Further preclinical and clinical studies are warranted to validate these results. https://ijbms.mums.ac.ir/article_27573.html Objective(s): Rheumatoid arthritis (RA) is a chronic autoimmune disease with progressive cartilage erosion and joint destruction. CD73 plays a critical role in regulating inflammatory responses. This study aims to investigate the effects of CD73 blockade on RA progression and explore the potential mechanism.Materials and Methods: Soluble CD73 levels were determined by enzyme-linked immunosorbent assay. Immunohistochemistry (IHC) was used to detect CD73 expression in tissues. A collagen-induced arthritis (CIA) rat model was used to evaluate the effect of CD73 inhibitors in vivo. Hematoxylin and eosin staining was used to evaluate synovial tissue inflammation. Safranin O/Fast Green staining and Micro-CT were used to evaluate cartilage erosion and bone destruction. A live cell imaging system was used to analyze cell proliferation. Cell invasion experiments were performed using Transwell chambers. Results: Our data showed that CD73 expression was significantly increased in synovial tissues and serum from RA patients. The increased CD73 expression may be attributed to the hypoxic microenvironment via the hypoxia-inducible factor pathway in synovial tissues. Using CIA rats, our data demonstrated that CD73 blockade alleviated bone destruction and synovial inflammation. CD73 blockade inhibited synovioblast proliferation, invasion, and pro-inflammatory cytokine production. Moreover, transcriptome analysis revealed that differentially expressed genes (DEGs) in synovioblasts induced by CD73 blockade were primarily enriched for inflammatory responses, neutrophil chemotaxis, and integrin-mediated signaling pathways.Conclusion: CD73 blockade alleviated RA disease progression by regulating the activity of synovial fibroblasts. CD73 blockade is a potential therapeutic approach for patients with RA. https://ijbms.mums.ac.ir/article_27477.html Objective(s): Platelet-rich plasma (PRP) is widely used in regenerative medicine due to its high concentration of bioactive growth factors; however, its short shelf life limits its clinical applicability. Lyophilization has been proposed to extend PRP stability, but its impact on biological efficacy remains unclear. This study evaluated whether lyophilization alters the biochemical composition and regenerative function of PRP derived from expired platelet units unsuitable for transfusion.Materials and Methods: Pooled isogroup PRP was processed as either liquid PRP or lyophilized PRP. Growth factors (FGF-1, PDGF, VEGF) and endotoxin levels were quantified. Biological activity was assessed in human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs) using MTT assays, in vitro wound closure, gene expression analysis (MMP-1, MMP-3, Ang1, PDGFR), and CD31 immunocytochemistry at 5% and 10% concentrations, with fetal bovine serum (FBS) as a control.Results: Lyophilization resulted in moderate reductions in FGF-1, PDGF, and VEGF relative to Liquid-PRP (P<0.05), while endotoxin levels remained acceptable. In HDFs, liquid-PRP induced higher MMP-1 and MMP-3 expression, whereas lyophilized-PRP promoted lower but sufficient expression, consistent with controlled extracellular matrix remodeling, with comparable wound-closure outcomes between PRP groups. In HUVECs, lyophilized PRP preserved cell viability, migration, and CD31 expression, comparable to liquid PRP and FBS. Angiogenic gene expression showed a concentration-dependent response, with maximal activation at 5% PRP, and no functional impairment after lyophilization (P<0.05).Conclusion: Despite a moderate reduction in growth factors, lyophilized PRP retained regenerative efficacy, supporting lyophilization as a viable strategy for the stable, sustainable reuse of PRP. https://ijbms.mums.ac.ir/article_27555.html Objective(s): Paclitaxel (PTX) is a commonly used chemotherapeutic agent that causes cardiotoxicity characterized by oxidative stress, inflammation, and mitochondrial dysfunction, which disrupts autophagy and apoptosis in cardiomyocytes. This study investigated the therapeutic potential of eugenol (EUG), a natural anti-oxidant and anti-inflammatory compound, against PTX-induced cardiac damage.Materials and Methods: Thirty-six male Wistar rats were randomly assigned to six groups: Control, EUG5, EUG25, PTX, PTX+EUG5, and PTX+EUG25. Hemodynamic parameters (systolic and diastolic blood pressure and heart rate), serum cardiac biomarkers (troponin T and brain natriuretic peptide), histopathological alterations, and immunohistochemical expression of autophagy-related proteins (mTOR, ULK1, and Atg13) were evaluated.Results: PTX administration significantly reduced arterial blood pressure and increased serum cardiac injury biomarkers, accompanied by marked myocardial structural damage. Histopathological analysis revealed myocardial degeneration, inflammation, edema, and tissue disorganization in the PTX group. In PTX-exposed rats treated with EUG, arterial blood pressure was higher, and serum cardiac injury biomarkers were lower than in the PTX group, accompanied by reduced histopathological scores. PTX exposure was associated with decreased mTOR expression and increased ULK1 and Atg13 immunoreactivity, while EUG-treated PTX groups showed values closer to those of the control group for these autophagy-related markers.Conclusion: EUG administration was associated with reduced biochemical and histopathological indicators of cardiac injury in PTX-exposed rats, along with changes in autophagy-related markers. These findings demonstrate that EUG treatment coincided with attenuation of PTX-induced cardiac injury at the biochemical and histopathological levels, suggesting its potential experimental value in models of chemotherapy-associated cardiotoxicity. https://ijbms.mums.ac.ir/article_27554.html Objective(s): Traumatic brain injury (TBI) induces oxidative stress, contributing to secondary neuronal damage. This study aimed to elucidate the role of the stress-responsive kinase HIPK2 in regulating endogenous antioxidant defenses in neural tissue following TBI.Materials and Methods: We employed complementary in vitro and in vivo models: an H₂O₂-induced oxidative stress model in PC12 cells (with HIPK2 inhibited by tBID) and a controlled cortical impact mouse model of TBI (with HIPK2 overexpressed via intracerebroventricular Ad-HIPK2 injection). Analyses included assessments of cell viability, mRNA expression, and protein levels of key antioxidant factors (HO-1, UGT1A1, NQO1).Results: In vitro, HIPK2 inhibition markedly increased oxidative stress-induced cell death and significantly down-regulated UGT1A1 expression. In vivo, endogenous HIPK2 expression was significantly suppressed post-TBI. Conversely, HIPK2 overexpression effectively rescued the expression of antioxidant proteins UGT1A1 and NQO1. Conclusion: These results demonstrate that HIPK2 is a critical modulator of the antioxidant response after TBI, capable of orchestrating key defense genes and conferring neuroprotection. Our findings identify HIPK2 as a promising molecular target for therapeutic intervention against TBI-related oxidative damage. https://ijbms.mums.ac.ir/article_27671.html Objective(s): Colorectal cancer remains a leading cause of cancer-related deaths worldwide, emphasizing the need for novel therapeutic strategies. Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, and retinol, a vitamin A derivative with antioxidant properties, have shown anti-cancer activity individually. This study investigates the combined effects of EGCG and retinol on human colorectal cancer cell lines, Caco-2 and HCT-116.Materials and Methods: Cytotoxic effects of EGCG and retinol, alone and in combination, were evaluated using resazurin-based cell viability assays. Intracellular reactive oxygen species (ROS) levels were measured by DCFDA assay to assess antioxidant activity. Changes in expression of apoptosis- and survival-related genes (p53, p21, AKT, and NF-κB) were analyzed using quantitative real-time PCR (RT-qPCR).Results: Combined treatment with EGCG and retinol reduced cell viability and intracellular ROS levels in both Caco-2 and HCT-116 cells. This treatment also modulated gene expression by increasing pro-apoptotic markers (p53 and p21) and decreasing anti-apoptotic markers (AKT and NF-κB), suggesting enhanced regulation of apoptosis-related pathways and inhibition of survival signaling.Conclusion: The combined effects of EGCG and retinol result in enhanced cytotoxicity, antioxidant activity, and modulation of apoptosis- and survival-related genes in colorectal cancer cells, supporting their potential as a combined therapeutic approach. Further studies are required to confirm these findings and explore clinical relevance. https://ijbms.mums.ac.ir/article_27672.html Objective(s): Parkinson’s disease (PD), a progressive neurodegenerative condition, involves the degeneration of dopaminergic neurons and the aggregation of α-synuclein (SNCA); however, the molecular mechanisms of this disorder remain incompletely understood.Materials and Methods: This study explores the role of the long non-coding RNA NEAT1 in PD by employing CRISPR/Cas9-mediated knockout in SH-SY5Y neuroblastoma cells treated with 6-hydroxydopamine (6-OHDA).Results: Deletion of NEAT1 was associated with increased cellular viability, attenuated both cytotoxicity and apoptosis, and elevated total antioxidant capacity (TAC), alongside a marked down-regulation of SNCA expression. Mechanistically, NEAT1 knockout was accompanied by increased hsa-let-7a-5p and decreased miR-506-3p expression, suggesting its function as a competing endogenous RNA (ceRNA) in miRNA-mediated stress pathways. Tyrosine hydroxylase (TH) levels remained unchanged, indicating that NEAT1 may influence neurotoxicity through post-transcriptional mechanisms.Conclusion: These results suggest NEAT1 is a crucial modulator of neurotoxicity in PD, with its inhibition offering therapeutic promise. Despite the in vitro nature of this study, our findings provide foundational insight into NEAT1’s dualistic roles in neurodegeneration and underscore its potential as a therapeutic target in PD. https://ijbms.mums.ac.ir/article_27686.html Objective(s): Huanglian Jiedu decoction (HLJDD), a classic traditional Chinese medicine formula, is investigated for its protective effects against Alzheimer’s disease (AD). This study explored its mechanism in an AD cell model, focusing on calcium ion (Ca²⁺) homeostasis regulation via mitochondria-associated endoplasmic reticulum membranes (MAMs).Materials and Methods: Mouse hippocampal HT22 cells were induced with 10 μmol·L⁻¹ Aβ₁₋₄₂ to establish the AD model, then divided into blank, model, and 15% HLJDD-containing serum intervention groups. Fluorescent dyes, qRT-PCR, western blotting, laser scanning confocal microscopy, and Annexin V-FITC/PI staining were used to detect intracellular reactive oxygen species (ROS), mitochondrial membrane potential, VDAC1/GRP75/IP3R (mRNA/protein levels), MAMs formation, intracellular Ca²⁺, and cell apoptosis, respectively.Results: Aβ₁₋₄₂ reduced HT22 viability in a concentration-dependent manner, while HLJDD significantly improved viability. Compared to the model group, HLJDD evidently decreased ROS levels (P<0.001), elevated mitochondrial membrane potential (P<0.001), up-regulated GRP75  (mRNA/protein, P<0.05), down-regulated VDAC1/IP3R (mRNA/protein, P<0.05 or P<0.001), reduced MAMs (via lower ER-mitochondria co-localization, P<0.05), alleviated Ca²⁺ overload  (P<0.001), and lowered apoptosis.Conclusion: HLJDD exerts protective anti-AD effects likely by reducing MAMs formation to alleviate intracellular Ca²⁺ overload, thereby lessening cell damage and apoptosis. https://ijbms.mums.ac.ir/article_27688.html Objective(s): This study aimed to evaluate the cytotoxicity and hepatoprotective effects of human umbilical cord mesenchymal stem cell–derived secretome (hUCMSC-Sec) in lipopolysaccharide (LPS)-induced HepG2 cells as an in vitro model of liver inflammation.Materials and Methods: hUCMSC-Sec was obtained from conditioned media of hUCMSCs at passage four. Inflammation was induced in HepG2 cells using LPS. Cytotoxicity was assessed using the WST-8 assay. Hepatoprotective effects of hUCMSC-Sec at concentrations of 12.5%, 4.17%, and 1.39% were evaluated by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), and tumor necrosis factor-alpha (TNF-α). Gene expression levels of α-smooth muscle actin (α-SMA), SMAD-7, collagen type I alpha 1 (COL1A1), and matrix metalloproteinase-1 (MMP-1) were analyzed using quantitative real-time PCR.Results: hUCMSC-Sec concentrations ranging from 1.6% to 25% were non-toxic, maintaining cell viability above 90%. Treatment with hUCMSC-Sec significantly reduced ALT, AST, GGT, and TNF-α levels in LPS-induced HepG2 cells. In addition, hUCMSC-Sec down-regulated α-SMA, COL1A1, and MMP-1 expression, while up-regulating SMAD-7 expression. The concentration of 4.17% showed the most pronounced hepatoprotective effect.Conclusion: hUCMSC-derived secretome demonstrated hepatoprotective effects by attenuating inflammatory and fibrotic responses in LPS-induced HepG2 cells. However, as this study was limited to an in vitro model, further in vivo and clinical studies are required to confirm its therapeutic potential and translational applicability.   https://ijbms.mums.ac.ir/article_27700.html Objective(s): Hepatic encephalopathy (HE) is a brain disorder linked to hyperammonemia from liver injury. Elevated ammonia levels are known to impair mitochondrial function, the primary energy source for cells. Therefore, this study aimed to evaluate energy-related signaling pathways enhancing mitochondrial biogenesis using thymoquinone (TQ) in an HE model.Materials and Methods: Wistar rats were randomly divided into three groups: sham, HE (200 mg/kg thioacetamide (TAA) in 2ml saline, administered intraperitoneally (IP) once every 48 hr for 14 consecutive days), and HE + TQ (20 mg/kg, IP, in 2 ml DMSO 5% administered once daily for seven consecutive days). Mitochondrial biomarkers (membrane potential [MMP], oxidative stress), gene expression (AMPK, PGC-1α), and protein expression (AMPK, P-AMPK, SIRT3, ANT1, CYPD, DRP1, VDAC, and P53) were measured in brain tissue. Additionally, electroencephalogram (EEG) recordings were obtained from the dentate gyrus (DG).Results: Our findings indicate that TQ was associated with a significant increase in MMP and a concomitant decrease in mitochondrial oxidative stress. Furthermore, TQ appeared to augment the AMPK/PGC-1α/SIRT3 signaling pathway, and was associated with the reversal of HE-induced down-regulation of ANT1 and VDAC, as well as up-regulation of CYPD, DRP1, and P53. Besides, TQ treatment was also linked to increased power recorded in the EEG from the DG region of the rat hippocampus.Conclusion: The AMPK/PGC-1α/SIRT3 signaling pathway appears to function as a key energy sensor that may help revitalize the metabolic machinery in mitochondria, potentially facilitating metabolic exchanges and energy production, particularly in response to neurodegenerative diseases such as HE. https://ijbms.mums.ac.ir/article_27701.html Objective(s): Allergic contact dermatitis (ACD) is a T cell-mediated type IV hypersensitivity reaction to haptens. Its pathogenesis involves keratinocyte dysfunction and dysregulation of the Signal Transducer and Activator of Transcription 3 (STAT3)-signaling pathway. However, the specific role of keratinocyte produced STAT3 in ACD remains unclear. To investigate the effect of keratinocyte (KC)-specific STAT3 conditional knockout on 1-Chloro-2,4-dinitrobenzene (DNCB)-induced ACD in mice.Materials and Methods: We generated keratinocyte-specific STAT3 conditional knockout (cKO) mice (K14-Cre⁺; STAT3flox/flox) and subjected them to DNCB-induced ACD, with STAT3flox/flox littermates as controls. Epidermal barrier function (transepidermal water loss and electrolyte permeability), histopathological inflammation (H&E and toluidine blue staining), and expression of inflammatory mediators (IL-1β, IL-6) were assessed. In vitro, STAT3 was knocked down by siRNA in HaCaT keratinocytes prior to stimulation with TNF-α/IFN-γ, followed by evaluation of inflammatory markers and STAT3 phosphorylation.Results: Keratinocyte-specific STAT3 deletion significantly ameliorated ACD severity, evidenced by reduced TEWL values, enhanced epidermal barrier function, decreased dermatitis scores, reduced clinical dermatitis scores, decreased dermal inflammatory infiltration, lower spleen index, and attenuated mast cell degranulation. Molecular analysis revealed down-regulation of inflammation-related factors (IL-1β, IL-6, TNF-α, JAK2) and significant inhibition of STAT3 phosphorylation. In vitro, STAT3 knockdown significantly suppressed IL-1β, IL-6, JAK2, Caspase-3, and MMP-3 expression in HaCaT cells and reduced STAT3 phosphorylation.Conclusion: Keratinocyte-specific STAT3 deletion alleviates epidermal barrier impairment and skin inflammation in ACD by inhibiting STAT3 phosphorylation and its downstream pro-inflammatory signaling.