Nitric oxide (NO) is a multifaceted signaling molecule with important roles in both prokaryotic and eukaryotic systems. In bacteria, NO is produced endogenously through several biochemical pathways, including the enzymatic activity of bacterial NO synthases (bNOS) and the respiratory denitrification enzymes known as nitrite reductases (NirK and NirS). These systems contribute to bacterial energy metabolism, stress responses, and intercellular signaling. Depending on its concentration, source, and biological context, bacterial NO may promote biofilm formation and antibiotic tolerance, whereas host-derived NO can contribute to bacterial clearance. Major bacterial genera reported to produce NO include Bacillus subtilis, Deinococcus radiodurans, Geobacillus stearothermophilus, Lactobacillus fermentum, and Staphylococcus aureus, as well as Neisseria, Haemophilus, Veillonella, Granulicatella, and Prevotella spp. Recent advances in molecular biology and synthetic biology have greatly expanded the repertoire of available approaches for engineering bacteria to produce NO at high or controllable biological levels. For example, Escherichia coli Nissle 1917 and Lactobacillus species have been engineered to express inducible NOS enzymes under tightly regulated promoters. Engineered therapeutics, including selective bNOS inhibitors, nanoparticle-delivered NO donors, and NO-antibiotic synergistic regimens, may harness this duality for therapeutic benefit. To exploit concentration-dependent effects that trigger biofilm dispersal at nanomolar levels followed by bactericidal bursts, next-generation NO-based therapies will need to achieve precise spatial and temporal control. Key areas of progress include decoding how bacteria detect NO from both host and self, engineering smart biomaterials that release NO in response to the infection microenvironment, and developing bNOS inhibitors that selectively target bacterial isoforms. In addition, modulation of NO in conjunction with other gasotransmitter systems, such as H₂S and CO, together with NO-sensing probiotic therapeutics and synthetic biology approaches, may offer promising strategies for improving NO production and therapeutic application.
Background & Objectives: Although exercise is widely recommended as a first-line intervention for osteoarthritis (OA), the relative effectiveness of specific exercise modalities remains unclear. This study aimed to examine the effects of hydrotherapy on motor function and selected psychological health indicators in women diagnosed with knee osteoarthritis (KOA). Materials & Methods: This quasi-experimental study employed a pre-test–post-test control group design and included 40 women with KOA (mean age = 56.5 years) who were selected through purposive sampling. Participants were assigned to either a hydrotherapy group (HG, n = 20) or a control group (CG, n = 20). The HG completed an eight-week hydrotherapy program based on the prescribed protocol, consisting of three 60-minute sessions per week. Outcome measures included the Osteoarthritis Research Society International (OARSI) physical function tests, the Visual Analogue Scale (VAS) for pain, the Tampa Scale of Kinesiophobia (TSK), and the 32-item Brunel Mood Scale (BRUMS). Data were analyzed using multivariate analysis of covariance (MANCOVA) in SPSS version 26, with statistical significance set at p < 0.05. Results: Following the intervention, the HG demonstrated significant reductions in the durations of the Timed Up and Go (TUG) test (ES = 0.89), the 40-Meter Walk (40MW) test (ES = 0.91), and the Stair Climb Test (SCT) (ES = 0.33) (p < 0.05). Moreover, the HG showed marked reductions in pain (F = 313.07, p = 0.002, ES = 0.61), kinesiophobia (F = 271.40, p = 0.001, ES = 0.89), and mood disturbance (F = 49.66, p = 0.001, ES = 0.27). Conclusion: Hydrotherapy significantly improved motor performance and psychological well-being in women with KOA. These findings support the integration of aquatic exercise as an effective therapeutic and preventive strategy for managing KOA.
Background & Objectives: Electroconvulsive therapy (ECT) is a medical intervention primarily used in the treatment of psychiatric disorders such as refractory major depression, refractory bipolar disorder, and refractory schizophrenia among patients not responding to other therapeutic modalities. The present study aimed to examine treatment adherence and life satisfaction among psychiatric patients receiving ECT. Materials and Methods: This descriptive-analytical, cross-sectional study was conducted in 2024 and included 200 psychiatric in-patients undergoing electroconvulsive therapy at Shariati Hospital in Fasa, southern Iran. Participants were selected through convenience sampling. Data were collected using three instruments: a demographic questionnaire, the Diener Satisfaction with Life Scale (SWLS), and the Treatment Adherence Questionnaire developed by Fatemi et al. Statistical analysis was performed using SPSS version 25, with multiple regression analysis and Pearson’s correlation coefficient used to examine the relationships among variables. Results: Among the participants, 66% (n = 132) were male and 34% (n = 68) were female. The mean scores for treatment adherence and life satisfaction were 80.02 ± 29.7 and 20.4 ± 8.03, respectively. No significant correlation was found between treatment adherence and life satisfaction (r = -0.086, p = 0.22). However, a significant positive correlation was observed between treatment adherence and the number of ECT sessions (r = 0.13, p = 0.05). Conclusion: In light of these findings, clinicians and mental health practitioners are encouraged to adopt evidence-based frameworks designed to promote treatment adherence, thereby improving patient outcomes and enhancing overall life satisfaction. Failure to address adherence, particularly among vulnerable patient subgroups, may lead to substantial personal and social consequences.
Houmansadr and Soleimani (2025) have provided valuable field-derived evidence supporting glpQ-LAMP as a pragmatic, economical, and sensitive approach for TBRF monitoring in tick vectors (4). Given that TBRF cases continue to be documented in Iran, with 1,415 cases recorded between 1997 and 2006, especially in the provinces of Ardabil, Hamedan, Zanjan, and Kurdestan, integrating LAMP into regional health laboratories could improve vector surveillance and ultimately reduce diagnostic delays (5). Future studies should therefore focus on validating this technique in clinical specimens obtained from febrile patients living in the same endemic foci, while also incorporating sequencing-based confirmation of discordant samples and systematic assessments of analytical specificity against co-circulating tick-borne pathogens.
Background & Objectives: Population aging is frequently accompanied by chronic disease trajectories and cumulative functional and psychosocial losses, all of which can undermine older adults’ overall sense of comfort. In this population, comfort is a fundamental human need that healthcare providers are ethically and professionally obliged to promote through intentional care strategies. Materials & Methods: This multicenter cross-sectional study aimed to translate the Comfort Measuring Scale into Persian and examine its psychometric properties for use among Iranian older adults with chronic conditions. The instrument’s measurement characteristics, including validity and reliability, were evaluated in accordance with COSMIN standards. Results: Item-level CVI scores ranged from 0.87 to 1.00, and the scale-level CVI was 0.96. Exploratory factor analysis identified a five-factor structure comprising Self-realization and Belonging, Normality of Life, Spirituality and Meaning of Life, Control, and Safety. Factor loadings ranged from 0.64 to 0.92, exceeded the conventional threshold for factor retention, and accounted for 67.78% of the total variance, thereby meeting the predefined adequacy criteria. Subsequent confirmatory factor analysis supported the proposed factor structure and demonstrated excellent goodness-of-fit indices (χ²/df = 1/109, RFI = 0.641, GFI = 0.951, RMSEA = 0.021, CFI = 0.951, NFI = 0.665, TLI = 0.948, PCFI = 0.888, and PNFI = 0.620). The scale also showed strong internal consistency, with a Cronbach’s alpha of 0.90 for the full instrument. Conclusion: The Persian version of the Comfort Measuring Scale demonstrated robust psychometric properties, supporting its use for assessing comfort among older adults with chronic conditions.
Background & Objectives: Alkaloids constitute a structurally diverse class of naturally occurring compounds with a wide range of pharmacological activities. One of the principal mechanisms through which alkaloids may contribute to the management of diabetes mellitus (DM) is the inhibition of α-glucosidase. Despite their considerable therapeutic potential, the molecular interactions between alkaloids and α-glucosidase remain insufficiently characterized and warrant comprehensive investigation. Therefore, this study aimed to identify potential alkaloid-derived α-glucosidase inhibitors using an in silico approach for the management of DM. Materials & Methods: An initial computational screening of 15 alkaloid ligands excluded cepharanthine because of predicted mutagenicity and immunotoxicity, whereas tetrandrine and fangchinoline were excluded because they failed to satisfy drug-likeness criteria. The remaining 12 compounds were subsequently subjected to molecular docking against α-glucosidase. Results: Scopolamine exhibited the most favorable docking score (-6.91 kcal/mol), outperforming acarbose, the reference inhibitor (-6.87 kcal/mol). In the α-glucosidase and scopolamine complex, Arg699 and Glu301 participated in hydrogen bond and Pi anion interactions, respectively. Secondary structure analysis further revealed scopolamine induced conformational alterations in α-glucosidase, characterized by an increase in α-helix content and a reduction in β-sheet content, changes that were consistent with its predicted inhibitory activity. Conclusion: These findings suggest that scopolamine is a promising candidate α-glucosidase inhibitor. Nevertheless, further in vitro and in vivo studies are required to validate its antidiabetic potential and determine its therapeutic value for controlling postprandial hyperglycemia in DM.
Background & Objectives: Uropathogenic Escherichia coli is the major causative agent responsible for urinary tract infections that contribute to a high percentage of community-acquired and nosocomial infections. The present study aimed to assess the effect of coumarin and quercetin on the expression level of gene encoding cytolethal distending toxin (cdt) from ciprofloxacin-resistant clinical isolates of uropathogenic E. coli. Materials & Methods: From a total number of 250 patient urine samples collected due to suspected UTI, 177 positive cultures for uropathogenic E. coli were isolated and 20 of which were positive for cdt gene. All the chemicals used for antibacterial activity assay were purchased from sigma Aldrich, and serial dilutions (0.125 to 1024 µg/mL) were prepared from stock solutions of coumarin and quercetin. The antibacterial activity of coumarin, quercetin, and ciprofloxacin was determined using broth microdilution. In addition, quantitative real-time polymerase chain reaction (qRT-PCR) was used to estimate the level of cdt gene expression. Results: Sub-inhibitory concentrations of coumarin (64 µg/mL) in combination with ciprofloxacin decreased the MIC and MBC values from 64 to 1 to 2 µg/mL and from 128 to 2 to 4 µg/mL, respectively. Similarly, sub-MIC concentrations of quercetin (32 µg/mL) combined with ciprofloxacin decreased the MIC and MBC values to 1 to 2 and 2 to 4 µg/mL, respectively. Additionally, the mean fold change of cdt gene expression level in treated uropathogenic E coli was lower than the untreated bacteria by 2.5-fold (1.9 to 3.0-fold; p < 0.001) in treatment with 64 µg/mL coumarin. The mean fold change of gene expression in the untreated isolates was 1.8 (0.9 to 2.0) fold higher than those treated with 32 µg/mL quercetin (p < 0.01). The reduction in gene expression was statistically significant in both tested treatments compared with the untreated control group. Conclusion: The obtained results demonstrated that coumarin and quercetin could be considered as antibacterial agents against uropathogenic E. coli and increase the antibacterial effect of ciprofloxacin while downregulating the expression level of cdt virulence determinant. It is recommended to perform more extensive experiments in vitro and in vivo to confirm the obtained results.
Background & Objectives: Asthma is a chronic inflammatory respiratory disease characterized by variable airflow limitation and bronchial hyperresponsiveness. Its prevalence is increasing, particularly in rapidly urbanizing regions, largely due to environmental and lifestyle transitions. This study aimed to estimate the prevalence of asthma and to identify associated demographic, occupational, and health-related risk factors in Fasa, Iran. Materials & Methods: In this cross-sectional study conducted between 2013 and 2017, a total of 353 adults from both urban and rural areas were enrolled. Data were collected using a standardized checklist covering demographic characteristics, occupation, educational attainment, marital status, smoking behavior, and comorbid conditions, including diabetes. Pulmonary function was assessed via spirometry, measuring FEV₁, FVC, FEV₁/FVC ratio, and PEF, in accordance with international guidelines. Results: Of the participants, 136 (38.5%) were male and 217 (61.5%) were female. Overall, females exhibited lower spirometric indices than males. The mean FEV₁ (L) and FVC (L) were 1.54 ± 0.85 and 2.63 ± 0.52 in females, compared with 2.61 ± 0.61 and 3.67 ± 0.33 in males, respectively, findings consistent with established sex-related differences in pulmonary function. Peak expiratory flow was also substantially higher in males (384.4 ± 13.15) than in females (267.1 ± 3.10). With respect to comorbidities, diabetes, hypertension, and heart disease were not significantly associated with asthma. In contrast, respiratory symptoms, including wheezing and shortness of breath, were significantly associated with asthma, with p-values ≤ 0.05 and ≤ 0.04, respectively. Conclusions: The findings suggest that the burden of asthma in Fasa is associated with gender, occupation, educational level, marital status, and diabetes. These results underscore the need for targeted public health interventions, including early diagnosis, patient education, and improved access to care. Further longitudinal studies with larger sample sizes are warranted to confirm these associations and to elucidate potential causal pathways.
For nearly a century, embryology was largely a descriptive science. We were careful and precise observers, but ultimately passive ones. Microscopic images, serial sections, and detailed fate maps taught us a great deal about what happens during development, yet they left one fundamental question unanswered: Could we actually intervene in this delicate, highly orchestrated process without disrupting its balance? Today, thanks to the convergence of nanotechnology and developmental biology, the answer has shifted from “perhaps” to a qualified but exciting “yes.” The emerging field I call nano-embryology has matured enough to tackle three profound challenges at once: How can we deliver molecular signals to the embryo with true spatial and temporal precision? How can we extract real-time information about the embryo’s internal state without causing harm? And, critically, might the nanoscale tools themselves pose risks to normal development? The first major advance comes from intelligent nanocarriers. These are no longer simple delivery vehicles. Engineered from light-sensitive lipids, pH-responsive polymers, or superparamagnetic iron oxide nanoparticles, they can release their cargo, such as key morphogens like Sonic Hedgehog or BMP4, not diffusely but at a specific location and moment within embryonic tissue. Imagine loading a neural differentiation factor onto such a particle and positioning it on the left side of a mouse embryo’s neural plate or during neural tube closure around embryonic day E8.0 to E9.0. A precisely timed near-infrared or magnetic stimulus then triggers release only in that region.
Background & Objective: Avian coccidiosis, caused by protozoan parasites of the genus Eimeria, imposes substantial economic losses on the global poultry industry. Rhoptry proteins (ROPs), as critical virulence determinants involved in host cell invasion, represent promising targets for vaccine development. This in silico study was designed to conduct a comprehensive immunoinformatic characterization of six key E. tenella ROPs in order to identify and prioritize potent T-cell and B-cell epitopes for rational vaccine design. Material & Methods: The physicochemical properties, antigenicity, allergenicity, solubility, and post-translational modification (PTM) sites of the six ROPs were systematically predicted using a suite of validated web-based tools. Secondary and tertiary structures were modeled, followed by rigorous refinement and validation procedures. Subsequently, cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes were predicted using human HLA allele surrogates. Their immunogenic potential, including the capacity to induce IFN-γ and IL-4 responses, was thoroughly evaluated. Linear B-cell epitopes were then identified and screened based on antigenicity, non-allergenicity, and optimal solubility profiles. Results: The findings demonstrated that all selected ROPs are antigenic, non-allergenic, and predominantly hydrophilic, with several exhibiting favorable solubility characteristics. Diverse PTM sites were identified, suggesting complex post-translational regulation. A repertoire of high-affinity and immunogenic CTL and HTL epitopes was detected, among which several candidates showed the potential to induce both IFN-γ (Th1) and IL-4 (Th2) responses, indicative of balanced immune activation. In addition, multiple linear B-cell epitopes with high antigenicity scores were identified. Conclusion: This study presents the first comprehensive bioinformatic blueprint of six E. tenella ROPs and highlights a rich pool of immunogenic epitopes for subsequent experimental validation and vaccine development.
Background & Objectives: Thyroid cancer is one of the most prevalent endocrine malignancies. Photodynamic therapy is an emerging minimally invasive therapeutic modality that employs a photosensitizer in conjunction with light irradiation to induce targeted cytotoxicity. The present study was designed to evaluate the effects of zinc phthalocyanine-mediated photodynamic therapy on the expression of immune checkpoint genes CD47 and SIGLEC15, as well as key genes involved in apoptotic pathways, in papillary thyroid cancer cells. Materials & Methods: The human papillary thyroid cancer cell line B-CPAP was exposed to various concentrations of zinc phthalocyanine and subsequently irradiated using a 675 nm diode laser at a fluence of 24 J/cm². Cellular viability, reflecting mitochondrial metabolic activity, was assessed using the MTT assay. The relative mRNA expression levels of CD47, SIGLEC15, Caspase-3, Caspase-9 and Bcl-2 genes were quantified using quantitative real-time polymerase chain reaction. Results: Zinc phthalocyanine-mediated photodynamic therapy markedly reduced the viability of B-CPAP cells. The treatment activated the intrinsic apoptotic pathway, as demonstrated by the significant upregulation of Caspase-3 and Caspase-9 transcripts alongside the downregulation of Bcl-2 expression. In addition, a statistically significant reduction in the mRNA expression levels of the immune checkpoint molecules CD47 and SIGLEC15 was observed following treatment. Conclusion: The findings of this study provide novel evidence that zinc phthalocyanine-mediated photodynamic therapy simultaneously induces apoptosis while downregulating the critical immune checkpoints CD47 and SIGLEC15 in thyroid cancer cells. This dual mechanism of action underscores the therapeutic potential of photodynamic therapy as an effective strategy for enhancing antitumor efficacy through both direct cytotoxic effects and the potential mitigation of immune evasion. Keywords: Thyroid cancer, Photodynamic therapy, Zinc phthalocyanine, Immune checkpoints, Apoptosis CD47 and SIGLEC15 Immune Checkpoint Genes Expression and Apoptotic Pathway Activation Following Photodynamic Therapy with Zinc Phthalocyanine in the B-CPAP Thyroid Cancer Cell Line Photodynamic Therapy, Immune Checkpoints, and Apoptosis in Thyroid Cancer Background & Objectives: Thyroid cancer is one of the most prevalent endocrine malignancies. Photodynamic therapy is an emerging minimally invasive therapeutic modality that employs a photosensitizer in conjunction with light irradiation to induce targeted cytotoxicity. The present study was designed to evaluate the effects of zinc phthalocyanine-mediated photodynamic therapy on the expression of immune checkpoint genes CD47 and SIGLEC15, as well as key genes involved in apoptotic pathways, in papillary thyroid cancer cells. Materials & Methods: The human papillary thyroid cancer cell line B-CPAP was exposed to various concentrations of zinc phthalocyanine and subsequently irradiated using a 675 nm diode laser at a fluence of 24 J/cm². Cellular viability, reflecting mitochondrial metabolic activity, was assessed using the MTT assay. The relative mRNA expression levels of CD47, SIGLEC15, Caspase-3, Caspase-9 and Bcl-2 genes were quantified using quantitative real-time polymerase chain reaction. Results: Zinc phthalocyanine-mediated photodynamic therapy markedly reduced the viability of B-CPAP cells. The treatment activated the intrinsic apoptotic pathway, as demonstrated by the significant upregulation of Caspase-3 and Caspase-9 transcripts alongside the downregulation of Bcl-2 expression. In addition, a statistically significant reduction in the mRNA expression levels of the immune checkpoint molecules CD47 and SIGLEC15 was observed following treatment. Conclusion: The findings of this study provide novel evidence that zinc phthalocyanine-mediated photodynamic therapy simultaneously induces apoptosis while downregulating the critical immune checkpoints CD47 and SIGLEC15 in thyroid cancer cells. This dual mechanism of action underscores the therapeutic potential of photodynamic therapy as an effective strategy for enhancing antitumor efficacy through both direct cytotoxic effects and the potential mitigation of immune evasion. Keywords:
Background & Objective: Urticaria is a common inflammatory skin disorder that, particularly in its chronic form, may result in substantial psychological and social consequences. Despite extensive evidence regarding mental health disturbances among affected individuals, the role of resilience as a psychological protective factor has remained insufficiently explored, particularly in comparative studies. This study aimed to compare mental health and resilience among patients with acute urticaria, patients with chronic urticaria, and healthy individuals. Materials & Methods: This causal-comparative study was conducted in Arak, Iran, between 2019 and 2020. A total of 90 participants were recruited through convenience sampling and equally assigned to three groups: patients with acute urticaria (n = 30), patients with chronic urticaria (n = 30), and healthy individuals (n = 30). Mental health was assessed using the Symptom Checklist-25 (SCL-25), while resilience was measured using the Connor-Davidson Resilience Scale (2003). Data were analyzed using multivariate analysis of variance (MANOVA) and Tukey’s post hoc test in SPSS version 20. Results: The findings indicated that patients with chronic urticaria exhibited the highest levels of mental health disturbances and the lowest levels of resilience compared with patients with acute urticaria and healthy individuals. In addition, patients with acute urticaria demonstrated poorer psychological status than healthy individuals across most domains. Conclusion: Chronic urticaria is associated with marked psychological vulnerability and diminished resilience. These findings underscore the importance of incorporating psychological screening, resilience-enhancing interventions, and patient education into the routine management of patients with chronic urticaria in order to improve long-term adaptation and quality of life.
Background & Objective: Burn injuries are inherently challenging to manage due to extensive tissue destruction and the substantial edema that ensues. This experimental animal study aimed to evaluate the synergistic effects of bacterial nanocellulose (BC) dressing combined with human umbilical vein endothelial cell-conditioned medium (HUVEC-CM) on the healing process of second-degree burn wounds in rats. Materials & Methods: Fifty male Wistar rats were randomly allocated into five groups: healthy control (no wound), negative control (untreated wounds, sham), BC dressing treatment, HUVEC-CM treatment, and combined BC plus HUVEC-CM treatment (n = 10 per group). A standardized burn wound with a diameter of 10 mm was created on the dorsal surface of each rat. The healing process was assessed macroscopically, using wound contraction percentage, and histopathologically over a 14-day period. Results: The combination group demonstrated the smallest wound area by day 3 and exhibited significantly enhanced wound closure on days 7 and 14 (p < 0.05). On day 3, wound closure percentages were as follows: negative control (-1.8 ± 1.7%), BC group (5.6 ± 2.1%), HUVEC-CM group (4.9 ± 2.4%), and combination group (9.1 ± 6.3%). The greatest degree of wound closure was observed in the combination group on day 14 (71.3 ± 6.8%). Histological analysis revealed that the combination treatment reduced early necrosis and inflammation, promoted granulation tissue formation and angiogenesis by day 7, and resulted in complete re-epithelialization by day 14. Conclusion: The combined application of BC and HUVEC-CM synergistically enhances burn wound healing by mitigating early tissue damage and promoting subsequent regenerative processes. This approach represents a promising bioactive strategy for advanced burn wound management.
The global obesity epidemic, affecting approximately 890 million adults, has catalyzed substantial advances in pharmacological management. Contemporary anti-obesity medications, including GLP-1 receptor agonists, dual GLP-1/GIP agonists, lipase inhibitors, and combination neurochemical modulators, can achieve weight reductions ranging from 5% to 22%, thereby approaching outcomes that were previously attainable only through bariatric surgery. Notwithstanding these therapeutic gains, a pronounced gap persists between clinical capability and real-world accessibility, as many of these novel agents remain prohibitively expensive or unavailable across large regions. Within this context, Iran’s pharmaceutical sector has demonstrated notable progress in the domestic production of several anti-obesity medications, including orlistat, marketed under more than 15 local brands, as well as metformin, liraglutide (Melitide, Maciza, Vikitide), tirzepatide (Spartina), and naltrexone/bupropion combinations (Lipoxon, Fandex). These developments have substantially enhanced treatment accessibility despite import restrictions and persistent cost barriers. However, rigorous head-to-head clinical trials comparing domestically manufactured products with their reference counterparts, alongside systematic post-marketing surveillance, remain indispensable for establishing long-term safety and therapeutic equivalence. In this regard, Iran’s experience delineates a viable model for expanding global access to obesity pharmacotherapy through localized manufacturing, with significant implications for health equity. Advances in Anti-Obesity Pharmacotherapy The obesity crisis has transitioned from a clinical concern to a defining global health challenge, with prevalence rates having tripled since 1975. Although lifestyle modification remains the cornerstone of management, its limited durability, evidenced by the fact that approximately 80% of individuals regain lost weight within one to five years, has rendered pharmacotherapy an essential component of comprehensive care. Increasing recognition of obesity as a chronic disease characterized by dysregulated neurobiological, metabolic, and hormonal pathways has fundamentally reshaped therapeutic paradigms over the past decade. Among recent developments, incretin-based therapies represent the most transformative advance. GLP-1 receptor agonists, such as liraglutide, which yields 5% to 8% weight loss, and semaglutide, associated with 15% to 17% reductions, achieve outcomes that previously required surgical intervention. The dual GLP-1/GIP agonist tirzepatide produces weight loss in the range of 20% to 22% and has demonstrated superiority over semaglutide in direct comparative studies; it has also recently received approval for the treatment of obstructive sleep apnea. Gastrointestinal adverse effects occur in approximately 40% to 50% of patients but are generally transient, whereas rare but serious risks include pancreatitis, occurring in 0.1% to 0.2% of cases, and gallbladder disease. Additional pharmacological classes include phentermine/topiramate, associated with 9% to 11% weight loss; naltrexone/bupropion, yielding 5% to 9%; and orlistat, which produces 5% to 10% weight reduction through inhibition of fat absorption. Precision therapies, such as setmelanotide, are indicated for specific genetic obesity syndromes. Furthermore, off-label use of metformin and SGLT2 inhibitors provides modest weight reduction, typically in the range of 1 to 3 kilograms, with well-established safety profiles. The Challenge of Equitable Access The principal challenge in obesity pharmacotherapy lies not in efficacy but in equitable access. In the United States, novel GLP-1/GIP agonists are priced between $900 and $1,400 per month, and many insurance plans exclude coverage for obesity medications; moreover, supply shortages continue to constrain availability. These factors give rise to substantial inequities, whereby individuals with adequate financial resources can access therapies capable of producing approximately 20% weight loss, while others remain limited to older, less effective treatments or receive no pharmacological intervention at all. Iran’s Domestic Production Capacity Iran’s domestic manufacturing capacity illustrates a viable alternative pathway. At least 15 locally produced orlistat brands are currently available, fostering price competition and enabling over-the-counter access. In 2023, metformin production exceeded 1.224 billion tablets. SinaGen Pharmaceutical manufactures liraglutide formulations (Melitide, Maciza, Vikitide) as bioequivalent prefilled pens approved by the Iran Food and Drug Administration. Most notably, the company introduced Spartina, a domestically produced tirzepatide, in early 2024, positioning Iran among the first countries outside the United States and Japan to achieve commercial production of this molecule. To contextualize affordability, Iran’s statutory monthly minimum wage in 2024 was approximately 7 to 8 million tomans. Consequently, the monthly cost of Spartina, estimated at 10 to 12 million tomans, corresponds to roughly 1.3 to 1.5 times the minimum monthly wage. Although this represents a considerable financial burden for many patients, it remains substantially lower than the $900 to $1,400 monthly cost of the originator product in the United States. In parallel, Danesh Pajoohan Arya Daro produces bioequivalent naltrexone/bupropion combinations (Lipoxon, Fandex), comparable to Contrave. Collectively, these advances have significantly improved both availability and affordability in the face of import constraints. Nevertheless, the full clinical value of domestically produced anti-obesity medications can only be established through rigorously designed head-to-head randomized controlled trials against originator products, complemented by structured post-marketing surveillance systems to assess long-term safety and sustained therapeutic equivalence. To date, no such comparative trials appear to be registered or underway in Iran. The establishment of a national pharmacovigilance framework, supported by registry-based surveillance, would therefore constitute a critical and achievable step toward generating high-quality evidence necessary for guideline integration and widespread clinical adoption. Implications for Global Health Equity and Future Directions This model carries important implications for global health equity. Regional collaboration could facilitate the consolidation of pharmaceutical production in countries with established manufacturing infrastructure, thereby serving multiple neighboring populations. Mechanisms such as technology transfer, voluntary licensing, biosimilar development, and differential pricing, all of which have proven effective in the context of HIV/AIDS treatment, could further accelerate the expansion of access. Looking ahead, the therapeutic pipeline remains robust. Emerging agents include triple incretin agonists, such as retatrutide, which has demonstrated approximately 24% weight loss in Phase 2 trials; oral small-molecule GLP-1 receptor agonists, including orforglipron, which may reduce production costs; long-acting monthly injectables; and next-generation MC4R agonists. However, the translation of these pharmacological innovations into meaningful population-level health outcomes will depend critically on overcoming the structural barriers that currently limit access and real-world effectiveness. In conclusion, contemporary obesity pharmacotherapy offers unprecedented therapeutic potential. Iran’s expansion of domestic pharmaceutical manufacturing provides a compelling model for addressing global disparities in access through localized production and technology transfer. Realizing this potential, however, will require parallel investment in rigorous comparative clinical trials and sustained post-marketing surveillance, as well as coordinated, systematic efforts to ensure equitable access for all patients, irrespective of geographic or economic constraints.
Background & Objectives: One of the established pharmacological strategies for slowing the progression of Alzheimer’s disease (AD) involves the inhibition of the acetylcholinesterase (AChE) enzyme. Current research has increasingly focused on the identification of novel compounds, particularly naturally derived metabolites, that exhibit potent modulatory activity alongside favorable toxicological profiles. In this context, diterpenoid alkaloids represent a promising therapeutic class for modulating AD pathology through AChE inhibition. Material & Methods: In this in silico study, molecular docking analyses were performed to screen and characterize diterpenoid alkaloids with the potential to attenuate AD progression. Results: Jesaconitine demonstrated a binding affinity of −6.72 kcal/mol, surpassing that of the reference inhibitor Tacrine (−6.21 kcal/mol). Docking simulations revealed critical interactions within the active site of AChE, including conventional hydrogen-bonding networks involving the residues Ser125, Asn87, and Tyr337. Conclusion: The findings of the present study identify Jesaconitine as a promising lead compound for the management of AD through AChE inhibition, based on in silico docking predictions. Moreover, these results provide a theoretical framework for the development of novel AChE inhibitors and indicate that Jesaconitine warrants further experimental and pharmacological investigation.
Background & Objectives: Noncommunicable diseases (NCDs) remain the leading cause of morbidity and mortality worldwide and are driven predominantly by modifiable lifestyle-related factors. In recent years, lifestyle medicine has emerged as a distinct clinical discipline and academic field at many leading universities, employing evidence-based lifestyle interventions to prevent, treat, and, in some cases, reverse chronic disease. This review examines the role of lifestyle medicine in the prevention and management of NCDs. Material & Methods: A narrative review was conducted using PubMed, Scopus, and Google Scholar to identify relevant literature published between 2000 and 2025. More than 130 studies, clinical guidelines, and position statements addressing lifestyle interventions, NCD outcomes, and implementation strategies were reviewed. Priority was given to systematic reviews, meta-analyses, randomized controlled trials, and large prospective cohort studies evaluating the six core pillars of lifestyle medicine and their implementation in clinical practice and public health settings. Results: Evidence across diverse study designs consistently demonstrates that whole-food, plant-predominant dietary patterns, regular physical activity, smoking cessation, reduced harmful alcohol consumption, restorative sleep, effective stress-management strategies, and strong social relationships are associated with a lower incidence and slower progression of major NCDs, as well as improved quality of life. Emerging evidence further supports the integration of lifestyle medicine into primary care, community-based interventions, and health-professional education. Conclusion: Current evidence supports lifestyle medicine as an effective and comprehensive framework for addressing the behavioral determinants of NCDs. As the field continues to expand clinically and academically, integrating lifestyle medicine principles into healthcare delivery systems and professional training programs may substantially strengthen the prevention and long-term management of chronic diseases.
Background & Objectives: This study aimed to evaluate serum thyroid hormone levels and thyroid histopathology following chronic whole-body exposure to 2.45 GHz Wi-Fi radiation in adult male Wistar rats using an estimated whole-body specific absorption rate (SAR). Materials & Methods: Twenty adult male Wistar rats (150 to 200 g) were randomly allocated to either the control group (n = 10) or the Wi-Fi exposure group (n = 10). The exposure group underwent continuous whole-body irradiation with a 2.45 GHz Wi-Fi signal for 24 h/day over a 30 day period. The estimated mean whole-body SAR in the exposed group was 1.4 W/kg (range: 1.2 to 1.6 W/kg). Serum concentrations of triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) were measured using radioimmunoassay. Thyroid tissues were subsequently processed for histopathological examination using hematoxylin and eosin staining. Statistical analyses were conducted using appropriate parametric or nonparametric tests, with statistical significance defined as p < 0.05. Results: Compared with the control group, rats exposed to Wi-Fi radiation exhibited significantly lower serum concentrations of T3 (1.73 ± 0.16 vs. 2.14 ± 0.17 ng/mL; p < 0.001), T4 (6.88 ± 0.19 vs. 7.38 ± 0.30 µg/dL; p = 0.003), and TSH (0.03 ± 0.01 vs. 0.05 ± 0.02 mIU/L; p = 0.014). Histopathological evaluation demonstrated reduced follicular diameter, manifested by the appearance of microfollicles, diminished colloid content, and disorganization of follicular epithelial cells in exposed animals relative to controls. Conclusion: Continuous exposure to 2.45 GHz Wi-Fi radiation at an estimated whole-body SAR of approximately 1.4 W/kg (range: 1.2 to 1.6 W/kg) for 30 days was associated with reduced serum T3, T4, and TSH concentrations, together with structural alterations in thyroid tissue in adult male rats.
The Long-Range Acoustic Device (LRAD) is increasingly employed in hybrid warfare due to its unique capability to generate highly directional sound waves. The physiological effects of LRAD exposure raise significant concerns, as such exposure can result in acute hearing damage, disequilibrium, and pronounced psychological stress. Sound levels produced by LRAD systems may exceed 160 dB, posing a substantial risk to auditory function and often causing severe discomfort or pain. Prolonged exposure has been associated with an elevated incidence of Post-Traumatic Stress Disorder (PTSD), with affected individuals experiencing flashbacks and heightened auditory sensitivity. Furthermore, the sensory overload and disorientation induced by LRAD emissions can impair decision-making capacity and situational awareness, thereby complicating crisis response. In conclusion, although LRAD serves a critical tactical function in contemporary hybrid conflicts, the well-documented risks of both acute and long-term psychological and physiological harm to combatants and non-combatants necessitate the urgent development of comprehensive operational guidelines and robust ethical frameworks. Such measures are essential to ensure that its deployment aligns with human rights standards and minimizes long-term collateral harm.
Background & Objective: The convergence of human cognition and artificial intelligence (AI) is reshaping cognitive identity and challenging traditional understandings of consciousness, agency, and selfhood. This narrative review introduces a conceptual three-stage model of cognitive hybridization, comprising Simulation, Integration, and Co-Evolution, to examine the dynamics of human-AI interaction and its neuroethical implications. Materials & Methods: Interdisciplinary evidence from cognitive neuroscience, AI research, and neuroethics was synthesized by drawing on studies published between 2000 and 2025 in PubMed, Scopus, and Web of Science. The review focused on brain-computer interfaces (BCIs), mechanisms of neural plasticity, and the cognitive capacities of large language models (LLMs). Results: In the Simulation stage, LLMs replicate selected cognitive operations such as language processing, although they lack any biological substrates, including hippocampal encoding and network-level neural dynamics. The Integration stage involves reciprocal interactions between the brain and AI, where BCIs facilitate emergent forms of shared agency mediated through cortical and basal ganglia pathways. The Co-Evolution stage reflects bidirectional adaptive processes that gradually reshape cognitive functions across both developing and aging brains. Key neuroethical considerations include autonomy, cognitive justice, and the protection of neural data and cognitive privacy. Conclusion: This model highlights the urgent need for updated theoretical and ethical frameworks that can guide human-AI co-evolution and promote equitable and safe cognitive enhancement. The proposed framework offers a structured foundation for future interdisciplinary inquiry in neuroethics and cognitive augmentation.
