Atopic dermatitis (AD) is driven by dysregulated cytokine signaling, oxidative stress, and eicosanoid-mediated inflammation, with current therapies offering incomplete control and safety concerns during long-term use. Metformin has recognized antioxidant and immunomodulatory actions, but its limited ability to traverse the skin barrier constrains topical application. Phosphatidylserine formulations may overcome this limitation by facilitating delivery and regulating inflammatory signaling cascades. To assess the therapeutic efficacy of phosphatidylserine-based metformin formulations (PS-Met) in an oxazolone-induced murine model. AD was induced in sixty-four female mice through topical oxazolone sensitization and challenge. Animals received 14 days of topical treatment with PS-Met at 0.5

BACKGROUND:Behçet's disease (BD) is a multisystem inflammatory disorder with variable manifestations. Although hepatic involvement is rare, abnormal liver enzymes may occasionally be observed. We describe two patients with BD who developed autoimmune hepatitis, confirmed by liver biopsy. CASE PRESENTATION:We report two Iranian patients - one male and one female - diagnosed with BD, who later developed persistently elevated liver enzymes. Both had elevated IgG levels, negative viral hepatitis markers, and liver biopsy findings compatible with autoimmune hepatitis. Due to limited retrospective serologic data, the diagnosis was established based on a multidisciplinary clinicopathological assessment and response to immunosuppressive therapy. Sonography showed fatty liver in both cases. Treatment with azathioprine and prednisolone led to the normalization of liver enzymes over a long-term follow-up. CONCLUSIONS:Although it is uncommon, AIH can co-occur with BD and should be considered in patients with persistently elevated transaminases. A liver biopsy is crucial for a definitive diagnosis. Early immunosuppressive therapy can prevent disease progression.

Background Better evaluation of the contribution of the main diseases, injuries, and risk factors for mortality and life expectancy is crucial for more efficient policy making at the national and subnational levels in Iran. The aim of this study is to assess the effect of emerging causes of mortality on health, specifically COVID-19, which can help policy makers implement preventive measures in similar situations. Methods In this systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we present estimates of cause-specific mortality at the national and subnational levels in Iran from 1990 to 2023. New to this iteration of GBD, we present a decomposition analysis of the contribution of specific causes of death to net gain or loss in life expectancy across 31 provinces of Iran. We used an array of data sources including censuses, vital registration, and surveys for national and subnational estimates. Findings The two leading causes of death in Iran were ischaemic heart disease and stroke in both 1990 and 2019. However, in 2020 and 2021, the COVID-19 pandemic displaced the leading causes of death, ranking first with age-standardised mortality rates of 286.2 deaths (95% uncertainty interval 267.9-310.5) per 100 000 in 2020 and 250.0 deaths (233.2-272.5) per 100 000 in 2021. COVID-19 ranked second and tenth in 2022 and 2023, respectively. Life expectancy at birth for both sexes combined declined from 78.0 years (77.7-78.1) in 2019 to 74.3 years (74.0-74.4) in 2020. It steadily recovered to 78.8 years (78.5-79.2) in 2023. COVID-19 was the main cause of loss in life expectancy, by 4.19 years, between 2019 and 2020. There was a net gain of 12.4 years in life expectancy in Iran from 1990 to 2023. The net gain at the national level can be mostly attributed to reduced mortality from ischaemic heart disease (2.61 years), stroke (1.63 years), neonatal disorders (1.26 years), transport injuries (0.88 years), and neoplasms (0.64 years). The decline in mortality rates of major causes continued to 2023 despite the pandemic. An exception was Alzheimer's disease, which showed a 4.0% increase in rate between 2019 and 2023 and led to a net loss of 0.04 years in life expectancy since 1990. Diabetes led to a net loss of 0.09 years since 1990. There were variations between provinces in terms of age-standardised rates and the net change in life expectancy before and after the COVID-19 pandemic. Interpretation The COVID-19 pandemic disrupted the rising trend of life expectancy in Iran, varying across provinces. Findings show that the health-care infrastructure and policies in Iran were not efficient in controlling the pandemic in 2020 and 2021, mainly due to inadequate vaccination coverage and timeliness, specifically for vulnerable subgroups. Sanctions may have aggravated the effect of COVID-19 on loss in life expectancy of Iranians. Despite the pandemic, the declining trend in age-standardised rates for top causes of mortality has continued to 2023, leading to a full recovery of life expectancy and underscoring the ultimate resilience of Iran's health system. Copyright (c) 2026 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Introduction:Ectopic Cushing's syndrome (ECS), a paraneoplastic syndrome resulting from tumors secreting adrenocorticotropic hormone (ACTH) or corticotropin-releasing hormone (CRH), often presents with severe hypercortisolism and rapid clinical deterioration. Identifying and surgically removing the ectopic source is crucial. We present a rare case of ECS originating from a neuroendocrine tumor of the kidney. Case presentation:A 36-year-old woman presented with generalized edema, muscle weakness, severe acne, hypertension, hyperglycemia, hypokalemia, and metabolic alkalosis, along with elevated ACTH and cortisol levels. The patient's condition was managed with ketoconazole, potassium supplementation, insulin, and antihypertensive medications while awaiting localization of the ACTH source. Dynamic pituitary magnetic resonance imaging (MRI) and chest computed tomography (CT) scans were unremarkable. An abdominal CT scan revealed bilateral adrenal cortical hyperplasia and a lesion in the left kidney, but a Gallium-68 DOTATATE positron emission tomography-computed tomography (PET/CT) scan did not show any avid lesions. En-bloc resection of the left kidney mass was performed. Immunohistochemical (IHC) staining confirmed a well-differentiated neuroendocrine tumor that was negative for ACTH but positive for cytokeratin, chromogranin, synaptophysin, insulinoma-associated protein 1 (INSM1), and paired-box gene 8 (Pax8). Postoperatively, the patient received hydrocortisone to prevent adrenal insufficiency, which was gradually tapered off. The serum levels of cortisol and ACTH returned to normal values. Hypokalemia, metabolic alkalosis, hypertension, and hyperglycemia resolved, and her general condition improved significantly. Discussion:Renal neuroendocrine tumors causing Cushing's syndrome are exceedingly rare. This case represents a unique instance of an ACTH-negative renal neuroendocrine tumor potentially secreting CRH that caused ECS. This case highlights the importance of considering renal tumors in the differential diagnosis of ECS.

Spinal cord injury (SCI) initiates a cascade of secondary injury mechanisms, including inflammation, oxidative stress, and neuronal degeneration, which severely limit functional recovery. Phosphatidylserine (PS), a critical phospholipid in neuronal membranes, has shown potential neuroprotective and anti-inflammatory effects in central nervous system injuries. This study evaluated the therapeutic efficacy and molecular mechanisms of PS at varying doses (10, 20, and 40 mg/kg) in a rat SCI model over 28 days, a model widely accepted as a reliable representation of human SCI, compared with methylprednisolone (MP) and control groups. Behavioral tests demonstrated dose-dependent improvements in locomotor function and a reduction in neuropathic pain in PS-treated rats, with the highest dose (40 mg/kg) producing effects comparable to those of MP. Histological analysis revealed that PS significantly decreased inflammatory infiltration, axonal degeneration, and cystic cavity formation, correlating with behavioral recovery. Molecular assays revealed that PS treatment significantly suppressed the pro-inflammatory cytokines TNF-α and IFN-γ, while restoring the levels of the anti-inflammatory cytokine IL-10. Furthermore, Western blot analysis showed that PS inhibited the phosphorylation of key signaling proteins in the MAPK (Mitogen-Activated Protein Kinase), ERK1/2 (Extracellular Signal-Regulated Kinase 1/2), and NF-κB (Nuclear Factor Kappa B) pathways, suggesting the attenuation of inflammatory signaling cascades. These results underscore the potential of PS as a therapeutic adjunct after SCI. By modulating inflammatory responses and intracellular signaling, PS preserves spinal cord tissue integrity and enhances functional recovery. This finding paves the way for the future application of PS as a promising adjunct to current pharmacological treatments for SCI, instilling optimism in the audience.

Background and Objectives: Thyroid carcinoma is a biologically heterogeneous malignancy, and the clinicopathological relevance of PD‑L1 expression remains unclear. This study aimed to assess PD‑L1 expression using TPS and CPS and to examine its association with clinicopathological features across different histological subtypes of thyroid carcinoma. Materials and Methods In this cross-sectional study, formalin-fixed paraffin-embedded tissue samples from patients with papillary, follicular, medullary, and anaplastic thyroid carcinoma were retrospectively collected from Imam Khomeini Hospital Complex. PD-L1 expression was assessed by immunohistochemistry and interpreted using TPS and CPS scoring systems. Clinicopathological data, including age, sex, tumor size, histological subtype, tumor stage, lymph node status, surgical margin involvement, and extrathyroidal extension, were extracted from pathology reports and medical records. Statistical analyses were performed to evaluate the association between PD-L1 expression and clinicopathological variables. Results A total of 100 patients were included, comprising 67 females and 33 males, with a mean age of 50.38 ± 16.13 years. PD-L1 expression assessed by both CPS and TPS showed significant variation across histological subtypes, with the highest expression observed in anaplastic thyroid carcinoma and the lowest in follicular and medullary carcinomas (p < 0.001). Higher PD-L1 expression was significantly associated with advanced tumor stage, surgical margin involvement, and extrathyroidal extension for both CPS and TPS. No significant association was observed between PD-L1 expression and patient sex. Conclusion PD-L1 expression in thyroid carcinoma is significantly associated with aggressive clinicopathological features and varies across histological subtypes. These findings suggest that PD-L1 may serve as a potential prognostic biomarker and support further investigation of immune checkpoint-based therapies in patients with advanced thyroid carcinoma.

Background/Objectives: Thyroid cancer (TC) is the most common type of endocrine neoplasm and is increasing in incidence, particularly papillary thyroid carcinoma (PTC). Early-stage disease has a favorable prognosis; however, advanced forms, such as anaplastic thyroid carcinoma, complicate treatment. Long non-coding RNAs (lncRNAs), longer than 200 nucleotides and non-coding, together with microRNAs, have emerged as major regulators of TC pathogenesis. This review summarizes data on how dysregulated lncRNAs influence the hallmarks of cancer in thyroid malignancies. Methods: We reviewed the literature on the role of lncRNAs and microRNAs in TC, focusing on their functions as competing endogenous RNAs (ceRNAs), regulators of PI3K/AKT and Wnt/β-catenin pathways, and controllers of epigenetic alterations. Results: Dysregulated lncRNAs contribute to hallmarks including sustained growth, evading suppressors, resisting death, replicative immortality, angiogenesis, invasion, metabolic reprogramming, immune evasion, genomic instability, and tumor-promoting inflammation. ceRNA mechanisms amplify immune evasion by regulating checkpoint proteins and cytokines, altering immune cell activity. Altered lncRNA profiles correlate with aggressiveness, metastasis, and prognosis. Notable lncRNAs, such as H19, MALAT1, and DOCK9-AS2, dysregulate oncogenic pathways and represent potential biomarkers. Conclusions: Advances in therapeutics suggest inhibiting oncogenic lncRNAs or restoring tumor-suppressive lncRNAs via RNA interference, antisense oligonucleotides, or CRISPR/Cas9 editing. New technologies, including single-cell RNA sequencing and spatial transcriptomics, will improve understanding of heterogeneous lncRNA–microRNA networks in TC and support precision medicine. LncRNAs signify both molecular drivers and clinical targets for thyroid cancer.

PURPOSE:Bone fracture is one of the most significant injuries of the body, which is usually caused by trauma. Astaxanthin (AST) showed beneficial effects on inflammation and oxidative stress, indicating protective effects on bone tissue. This study was performed with the aim of evaluating the effect of AST on the improvement of behavioral changes and the ossification process in the defect created in the femur of the rats. METHODS:Animals were randomly divided into 3 groups, sham (healthy), control (bone fracture), and treatment. The sham group received water and normal food. In the control group, the fracture of the femur (3 holes) was done through a dental drill. A group of animals was treated daily with AST (1 mg/kg) by intraperitoneal injection (i.p.) 24 h after surgery for 3 weeks. RESULTS:Behavioral tests (open field test and grid walk test) showed increased movement inconsistency and balance in the control group compared to the sham group. At the same time, treatment with AST for 3 weeks improved movement disorders in behavioral tests. The results of histological analysis and radiography showed that the treatment with AST led to decreased inflammation and necrosis and increased bone optical density. Fracture caused elevation in the levels of oxidative stress marker (MDA) as well as the pro-inflammatory cytokine (TNF-α and (IL-1β). However, treatment with AST reversed it. CONCLUSIONS:Based on the results from this study, AST, as an anti-inflammatory, and an antioxidant therapeutic agent, has therapeutic effects on bone fractures.

Follicular thyroid carcinoma (FTC) makes up about 10

Background & Objective:Adrenal tumors present a notable prevalence of 4-7% in individuals above 40 years old. Current guidelines recommend adrenalectomy for hormone-secreting, potentially malignant, or large (>4 cm) lesions. However, the outcomes of adrenalectomy and their clinical-pathological associations remain poorly defined. This study assessed adrenalectomy outcomes and explored its clinical, demographic, and pathologic correlates. Methods:In this retrospective cohort study, the medical records of all patients who underwent adrenalectomy from March 2016 to March 2021 at a referral center in Tehran were reviewed. Also, a clinical follow-up via telephone was conducted. The chi-square test, independent t-test, and analysis of variance were utilized for statistical analysis. Results:Data from a total of 75 patients (55 females) were reviewed. The mean age of the participants was 42.67 years. Of them, 60%, 22.7%, 14.7%, and 1.3% had pheochromocytoma, Cushing's syndrome, Conn's syndrome, and insulinoma, respectively. Malignancy was associated with greater tumor size (p<0.000) and mitotic rate (p=0.046), and the presence of necrosis (p=0.001), and capsular and vascular invasion (p<0.000). Clinical follow-up visits of 45 patients indicated 84.4% showed a complete response to the treatment (surgical ± medical). Treatment response was significantly influenced by approach (laparoscopic favored; p=0.001), surgery duration (<150 minutes better; p=0.017), mass pathology (adenoma favored; p=0.034), and capsular invasion (absence better; p=0.012). Conclusion:Adrenalectomy outcomes were significantly affected by surgical approach and tumor pathology, notably capsular invasion. Larger studies are needed to determine the predictive values of clinical and pathologic variables in adrenalectomy for adrenal tumors.

Ischemia–reperfusion injury remains a critical challenge in reconstructive surgery, often leading to extensive tissue necrosis and compromised skin flap survival. This study investigated the protective effects of licofelone, a dual cyclooxygenase and lipoxygenase inhibitor, in a rat model of random-pattern skin flap ischemia. Forty male Wistar rats underwent skin flap surgery following ischemia induction and were administered licofelone at doses of 1, 5, 10, or 20 mg/kg, with treatment given 30 min before surgery. The extent of flap necrosis was quantified 7 days postoperatively, while inflammatory markers, nitric oxide levels, and the expression of cyclooxygenase-2 and lipoxygenase-5 were assessed through enzyme-linked immunosorbent assay and western blotting. Histological evaluations were performed using hematoxylin and eosin and Masson’s trichrome staining. Licofelone at 10 mg/kg significantly reduced necrosis, with a median necrotic area of 18.15

Testicular torsion, a medical condition contributing to male infertility, results in severe scrotal pain and ischemia. Oxidative stress factors contribute to germ cell death following surgical reperfusion, suggesting postoperative pharmacotherapy could mitigate testicular ischemia/reperfusion (I/R) injury. Ivermectin, a GABA receptor modulator for treating parasitic infections such as onchocerciasis, has demonstrated anti-oxidative stress and anti-apoptotic properties. Therefore, this study aimed to evaluate the efficacy of ivermectin administration after detorsion using a rat model of testicular torsion/detorsion (T/D). This study utilized 40 male Wistar rats weighing 200-250 grams. The studied groups were the sham (no T/D induction), control (T/D and no treatment), and T/D following administration of ivermectin administration and the doses of 1, 2, and 5 mg/kg intraperitoneally. For I/R surgery, both testes were twisted 720 degrees clockwise for 4 h to cause torsion. Subsequently, the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) activity were assessed using ELISA, while the expression of GABAB receptors and apoptosis were examined using the immunohistochemical method. Histopathological alterations were evaluated with hematoxylin and eosin (H&E) staining to evaluate cell counts and seminiferous tubule diameters. Administration of ivermectin effectively reduced oxidative stress levels, as evidenced by decreased MDA levels and increased SOD activity, compared to the control group (P < 0.01 and P < 0.05, respectively). Ivermectin also modulated the expression of elevated GABAB receptors and caspase 3 (P < 0.05 and P < 0.001, respectively). Furthermore, histopathological analysis revealed that ivermectin prevented germ cell degeneration, edema, and hemorrhage in the testis (P < 0.05). Ivermectin may be a potential treatment option for protecting against testicular torsion and may have beneficial effects on mitigating germ cell death, oxidative stress, and GABAB receptor modulation. Further research is needed to explore dosages, long-term impacts, and clinical trials to determine the potential for patients with testicular torsion.

Anaplastic thyroid carcinoma (ATC) is a lethal subtype of thyroid cancer with a poor prognosis. Due to the lack of promising treatment opportunities for ATC, gaining a better understanding of the molecular mechanisms underlying tumorigenesis seems crucial. Here, we focused on two major players in the Wnt signaling pathway. The expression of PP2A and GSK3α/β proteins was studied in 12 ATC and 15 goiter formalin-fixed paraffin-embedded tissue samples using immunohistochemistry. The intensity of nuclear staining in tumor cells, as well as the total scores of protein expression, were calculated. The expression of inactive PP2A and active GSK3α/β proteins was negative in all control (goiter) samples. Both proteins were expressed in all ATC samples at different levels. Notably, eight samples represented strong expression (percentage = 100; total score = 300) of both proteins. The average total score staining was 210.3 for the phosphorylated and active form of GSK3α/β (Y279/216) and 274.5 for phosphorylated PP2A at Y307 and its inactive form. For features such as age, gender, greatest diameter of tumors, as well as PP2A and GSK3α/β total staining scores, no significant differences were observed between metastatic and nonmetastatic cases. Similarly, no association was demonstrated between metastasis with demographic and tumor characteristics. The current study investigated the expression of PP2A and GSK3α/β, two key proteins in the Wnt signaling pathway, in ATC tissue samples. Although this study highlights the importance of PP2A and GSK3α/β in ATC, a clear understanding of PP2A and GSK3α/β dysregulation and function in ATC remains to be elucidated.

BACKGROUND:Testicular torsion is a urological emergency requiring timely intervention to prevent irreversible damage, infertility, or orchiectomy. OBJECTIVE:To investigate the protective effects of lithium against testicular torsion/detorsion (T/D) damage in a rat model. METHODS:Seventy-two adult rats were randomly assigned to six groups: Group I: sham-operated control; Group II: lithium treatment with sham surgery; Groups III-VI: 4-h ischemia by 720° counterclockwise testis twisting, followed by 24-h reperfusion. Two hours before the onset of reperfusion, rats in Groups III-VI received vehicle or varying doses of lithium chloride (12, 30, or 60 mg/kg). We assessed oxidative stress, inflammation, and nitrosative stress biomarkers, glycogen synthase kinase-3β (GSK-3β) levels, and conducted histopathological examinations. RESULTS:Lithium showed remarkable protective effects against T/D injury, with 60 mg/kg being most effective. This dosage significantly reduced malondialdehyde, interleukin-6, tumor necrosis factor-α, and nitric oxide metabolite levels by 44 %, 78 %, 55 %, and 65 % compared to the vehicle group, respectively. It also inhibited GSK-3β by promoting Ser9 phosphorylation. Histopathological analysis revealed lithium treatment was effective in minimizing testicular damage, restoring testicular weight, and preserving the structural integrity of seminiferous tubules. CONCLUSION:Despite previous reports of lithium toxicity in testicular tissue, lithium treatment serves as a promising option to prolong the therapeutic window for intervention and protect against ischemia-reperfusion injury following surgical correction of testicular torsion.

Background Testicular torsion is a urological emergency that requires prompt surgery to prevent orchiectomy. Pharmacological interventions may slow the progression of damage and reduce reperfusion injury after surgical correction. Purpose This study evaluated the protective effects of linezolid against testicular torsion-detorsion (T/D) injury in rats by focusing on the mechanisms involving the Toll-like receptor 4 (TLR-4) pathway. Methods Eighty-four male Wistar rats were allocated into 8 groups; of them, one was subjected to a sham operation and another was subjected to 4-hour ischemia via 720° of torsion followed by 24-hour reperfusion. Linezolid (3–100 mg/kg) was assessed for its effects on T/D injury using histopathological evaluation, oxidative stress markers (malondialdehyde [MDA], superoxide dismutase [SOD]), and inflammatory biomarker tumor necrosis factor-alpha (TNF-α). Mechanistic investigations have focused on TLR-4 the mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) pathway. Molecular docking and in silico analyses were conducted to predict interactions with key inflammatory proteins. Results Linezolid 25, 50, and 100 mg/kg significantly reduced the histopathological damage, with 50 mg/kg being the most effective dosage. Within the 6–50 mg/kg range, linezolid reduced MDA, increased SOD, decreased TNF-α, and suppressed TLR-4/NF-κB pathway activity, with maximal reductions in MDA, TNF-α, NF-κB, and TLR-4 of 64%, 77%, 56%, and 53%, respectively, and an enhancement in SOD of 47%. In silico docking predicted strong binding interactions with TLR-4 pathway proteins, including p38 MAPK and JNK, with affinities of -7.4 to -8.3 kcal/mol. Conclusion Linezolid protects against testicular torsion by reducing oxidative stress and inflammation via modulating the TLR-4/NF-κB pathway, suggesting its therapeutic potential and need for further study.

Many studies have reported the aberrant expression of lncRNAs and indicated their role in cancer progression and drug resistance across various cancers. In this study, we aimed to evaluate the effect of LINC00162 lncRNA on the chemosensitivity of thyroid cancer cells, both individually and in combination with sorafenib, on various biological processes. In this regard, we conducted our experiments in several groups: (1) LINC00162 siRNA-transfected cells, (2) Sorafenib-treated cells, (3) Cells that received both siRNA transfection and sorafenib treatment (4) Control group. MTT assay results revealed that siRNA-mediated silencing of LINC00162 reduced the viability of the B-CPAP thyroid cancer cells and increased the sensitivity of these cells to sorafenib by reducing its IC50. Flow cytometry analysis of apoptosis and cell cycle progression indicated that LINC00162 silencing induced apoptosis and Sub-G1 cell cycle arrest, while its combination with sorafenib significantly increased the apoptosis rate and also arrested cells in the G2-M phase in addition to the Sub-G1 phase. This combination treatment increased the expression of apoptosis-related genes BAX, CASP3, CASP9 while decreasing BCL2 expression. Additionally, significant inhibition of the cell-cycle related genes MYC and Cyclin D and upregulation of TP53 were observed following combination treatment. Furthermore, the combination therapy reduced the migration of B-CPAP cells through the downregulation of MMP-3 and MMP-9. Colony sizes and numbers also decreased following siRNA-mediated silencing of LINC00162 and sorafenib treatment. qRT-PCR analysis of stemness-related genes, including NANOG, SOX2, CD44, and CD133 confirmed the findings of the colony formation assay. To understand the underlying mechanisms of LINC00162 lncRNA in thyroid cancer progression, we evaluated the expression of MAPK pathway genes. Our findings indicated that LINC00162 silencing, in combination with sorafenib, reduced the expression of MAPK, KRAS, and RAF genes. From our findings, we can conclude that LINC00162 silencing, both individually and combined with sorafenib, reduced the progression and viability of thyroid cancer cells through modulating genes involved in key pathways and could be considered a new therapeutic approach for the treatment of papillary thyroid cancer (PTC).

This study aims to develop and validate a predictive model for thyroid nodule malignancy risks using clinical and ultrasonography features and a machine learning (ML) approach. This retrospective study is based on the clinical and ultrasound characteristics of 1035 thyroid nodules (845 benign and 190 malignant) to develop and validate the risk prediction model. Employing multiple logistic regression, key features were selected in developing the model. Eight ML algorithms were evaluated for predicting the risks of malignancy. Finally, the predictive ability of the best-performing algorithm was compared against American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) and American Thyroid Association (ATA) guidelines. Based on AUC criteria (88.3, 95 https://aimedlab.ir/tnr .

Acute mesenteric ischemia-reperfusion is a life-threatening condition that causes severe intestinal injury through oxidative stress, inflammation, and apoptosis. Despite its high mortality rate, no pharmacological treatment is currently available to reduce tissue damage. This study aimed to evaluate the therapeutic potential of phosphatidylserine in a rat model of mesenteric ischemia-reperfusion and to explore its underlying mechanisms, with particular focus on the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. Thirty-six male Wistar rats were randomly assigned into six groups: sham, ischemia-reperfusion, and phosphatidylserine-treated groups at doses of 10, 20, and 40 mg/kg. Ischemia was induced by clamping the superior mesenteric artery for 60 min, followed by 60 min of reperfusion. Phosphatidylserine or vehicle was administered intraperitoneally 15 min before reperfusion. Ileal tissues were collected for histopathological evaluation, measurement of malondialdehyde, interleukin-6, glutathione peroxidase and superoxide dismutase activity, analysis of tumor necrosis factor-alpha, BAX, B-cell lymphoma 2, and assessment of Akt and mTOR phosphorylation by western blot. Reverse and molecular docking studies were conducted to identify potential targets of phosphatidylserine. Phosphatidylserine at 40 mg/kg significantly improved intestinal injury and modulated oxidative, inflammatory, and apoptotic markers. The findings support involvement of Akt/mTOR pathway and suggest phosphatidylserine as a potential therapeutic candidate.

Early detection of malignant thyroid nodules is crucial for effective treatment, but traditional diagnostic methods face challenges such as variability in expert opinions and limited integration of advanced imaging techniques. This prospective cohort study investigates a novel multimodal approach, integrating traditional methods with advanced machine learning techniques. We studied 181 patients who underwent fine-needle aspiration (FNA) biopsy, each contributing one nodule, resulting in a total of 181 nodules for our analysis. Data collection included sex, age, and ultrasound imaging, which incorporated elastography. Features extracted from these images included Thyroid Imaging Reporting and Data System (TIRADS) scores, elastography parameters, and radiomic features. The pathological results based on the FNA biopsy, provided by the pathologists, served as our gold standard for nodule classification. Our methodology, termed ELTIRADS, combines these features with interpretable machine learning techniques. Performance evaluation showed that a Support Vector Machine (SVM) classifier using TIRADS, elastography data, and radiomic features achieved high accuracy (0.92), with sensitivity (0.89), specificity (0.94), precision (0.89), and F1 score (0.89). To enhance interpretability, we used hierarchical clustering, shapley additive explanations (SHAP), and partial dependence plots (PDP). This combined approach holds promise for enhancing the accuracy of thyroid nodule malignancy detection, thereby contributing to advancements in personalized and precision medicine in the field of thyroid cancer research.

Introduction Cirrhotic cardiomyopathy (CCM) is recognized by impaired cardiac responsiveness to stress, prolonged QT interval, and systolic and diastolic dysfunctions. Connexins are a family of transmembrane proteins that play a key role in cardiac physiology. Connexin 43 (Cx43) inhibition showed cardio-protective effects. Peptide drug Cx43 inhibitor, Gap 26, could inhibit gap junction 43. This study was designed to evaluate the effects of a connexin mimetic peptide, Gap 26, in the CCM model in rats. Methods The cirrhosis was induced through carbon tetrachloride (CCl4). On day 56, electrocardiography (ECG) was recorded, spleen weight was measured, and tissue and serum samples were collected. Further, Cx43 mRNA expression in heart tissue was checked. Results The chronotropic responses decreased in the CCl4/saline and increased in the CCl4/Gap. The spleen weight, QTc interval, and brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-α), aspartate aminotransferase (AST), alanine transaminase (ALT), and malondialdehyde (MDA) levels elevated in the CCl4/saline, and the spleen weight, QTc interval, and MDA and ALT levels were reduced by Gap 26 treatment. The level of nuclear factor (erythroid-derived 2) factor 2 (Nrf2) decreased in the CCl4/saline. The Cx43 expression was downregulated in the CCl4/saline and upregulated with the Gap 26 treatment. Conclusion Gap 26 not only alleviated the chronotropic hyporesponsiveness and the severity of liver damage and upregulated the atrial Cx43 expression, but it also had an antioxidant effect on the heart.