Abstract: Acidic cannabinoids (e.g., THCA, CBDA) are the dominant phytoconstituents in Cannabis Sativa and serve as precursors to neutral forms (THC, CBD) via decarboxylation. This is the third work in an integrated series exploring how dietary cannabis inputs interact with the Endocannabinoid System (ECS) pathways. This paper examines the role of physiological environments—specifically stomach acidity, blood pH, and hepatic metabolism—in determining the fate and bioavailability of ingested acidic cannabinoids.[Approach & Findings] Integrating organic chemistry and pharmacokinetics, the study confirms that gastric conditions (pH 1.5–3.5, 37°C) induce a minor, diet-dependent partial decarboxylation ($\leq 5-10\%$) due to the low activation energy at physiological temperature and poor solubility. Upon absorption, systemic blood pH (7.35–7.45) stabilizes the acidic cannabinoids, which exist primarily as non-decarboxylating carboxylate anions (>99% ionized). The hepatic first-pass metabolism then primarily processes the compounds through CYP and UGT enzymes, leading to conjugated metabolites (e.g., THCA-glucuronide) rather than extensive decarboxylation.[Microbiome & Implication] Crucially, the gut microbiome is identified as a secondary modulator, utilizing microbial decarboxylases and $\beta$-glucuronidases to potentially recycle cannabinoids via enterohepatic circulation, thus impacting systemic exposure and therapeutic effects. This comprehensive analysis integrates chemical kinetics and physiological variables, showing that acidic cannabinoids are delivered largely intact to modulate the ECS directly (e.g., THCA activating TRPA1; CBDA inhibiting FAAH).[Conclusion] The minor in vivo conversion rate means the therapeutic potential of ingested acidic cannabinoids is shaped more by direct ECS interaction and microbial/metabolic processing than by thermal decarboxylation.

Abstract:

Urolithin A (UA) is a gut microbiota-derived metabolite of dietary ellagitannins with anti-inflammatory, mitochondrial, and neuroprotective properties. Because systemic UA availability depends on specific microbial consortia, dysbiosis may lead to functional loss of urolithin production. Melatonin, assessed via its major urinary metabolite 6-sulfatoxymelatonin (6-SMT), has been linked to cancer risk modulation in epidemiologic studies. In this three-year pilot observational study in Caucasian adults, we compared Group 1 (n = 231) with aggressive stage IV tumors (colorectal, hepatic, pancreatic, NSCLC, SCLC, TNBC, or glioblastoma), Group 2 (n = 118) with less aggressive advanced tumors (stage IV ER/PR+++ HER2-negative breast cancer, WHO grade 2 astrocytoma, or stage IV carcinoid tumors), and healthy controls (n = 117). UA was quantified by HPLC in plasma and stool; stool microbiota were cultured with attention to Streptococcus thermophilus, Enterococcus faecium, and Bacteroidetes; serum IL-6, TNF-α, IL-8, and IL-10 and 24 h urinary 6-SMT were measured. Group 1 exhibited severe selective dysbiosis with loss of S. thermophilus and E. faecium and critical reduction in Bacteroidetes, accompanied by undetectable UA in plasma and stool, marked elevation of pro-inflammatory cytokines (IL-6, TNF-α, IL-8) with normal IL-10, and profoundly reduced 6-SMT. Group 2 showed an attenuated pattern (reduced but detectable UA, moderate dysbiosis, moderately elevated cytokines, and moderate 6-SMT reduction). We identify a reproducible dysbiosis-UA-melatonin triad associated with tumor aggressiveness and propose it as a candidate composite biomarker framework for prospective validation and mechanistic studies.

Abstract: Duchenne muscular dystrophy (DMD), Limb-girdle muscular dystrophies (LGMD), and GNE myopathy (GNEM) are progressive neuromuscular rare genetic diseases with differing etiologies either due to defects in structural muscle proteins or impaired metabolism and manifests through progressive weakening and deterioration of skeletal muscle tissues. This review summarizes current and recent clinical trials worldwide, highlighting curative approaches for neuromuscular diseases such as DMD, LGMD, and GNEM. We compiled and summarized latest and most promising outcomes from ongoing global clinical trials, using information from official websites, news sources, trial registries, databases and literature across four key therapeutic modalities: 1) palliative therapies: steroidal and non-steroidal 2) gene therapy and gene-targeted interventions, 3) cell-based regenerative strategies and 4) universal treatments (therapies not limited to the mutation type). We also highlighted the risks associated with gene therapy and discussed key regulatory considerations.Several current clinical trials show promise for muscular dystrophy treatments. RGX-202 gene therapy demonstrates early muscle strength improvement in DMD children. MyoPAXon, a stem cell therapy for DMD muscle regeneration, has FDA clearance to begin trials. Sevasemten (EDG-5506) trials report slowed DMD/BMD progression. SRP-9003 gene therapy targets protein restoration in LGMD. ACENOBEL, approved in Japan for GNEM, may delay disease progression if started early. These trials offer high potential to become widely available treatments improving quality of life and provide life-saving therapeutic options. Additionally, Indian specific founder mutations for the mentioned muscular dystrophies are highlighted to understand the disease etiology in Indian populations for precise diagnostics and therapeutics.

Abstract: Objectives: Retrograde menstruation occurs in most women and could cause some peri-toneal irritation. The peritoneal cavity is a cavity outside the bloodstream, with a specific hormonal, immunological and microbiological micro-environment distinct from plasma. The mesothelial cells lining the peritoneal cavity react within seconds to minor trauma, such as blood, with retraction, causing acute inflammation and later inflammation. This mesothelial cell retraction exposes the basal membrane and facilitates implantation of tu-mour cells. The acute inflammation enhances adhesion formation after surgery, and causes pain. Design: A systematic review of menstrual C-reactive protein (CRP) concentrations, a non-specific marker of peritoneal inflammation (PROSPERO ID 536306). Results: All articles (n=8) showed a variable increase in CRP concentrations during the men-strual and early follicular phase of 80±36%. Conclusions: CRP concentrations are slightly increased during menstruation and the early follicular phase. This increase is likely due to retrograde menstruation, causing mesothelial cell retraction and acute pelvic inflamma-tion. It seems logical that the mesothelial cell retraction facilitates endometrial cell im-plantation and explains the anatomical distribution of endometriosis lesions. Acute pelvic inflammation may enhance postoperative adhesion formation.

Abstract:

Spinal cord injury (SCI) is linked to a variety of negative outcomes and prognoses that can profoundly affect the lives of individuals, resulting in significant disruptions to multiple facets of their daily activities. A prominent secondary consequence of SCI is the onset of systemic infections, which may disseminate to other organs, including the kidneys, thereby impairing their functionality. Previous studies have demonstrated that the alcoholic extracts of Rosmarinus officinalis and Melissa officinalis possess antioxidant and neuroprotective properties, indicating their potential utility in the treatment and management of SCI and its associated secondary complications. Therefore, this study aimed to examine the combined effects of these extracts on sensory and motor functions, alterations in kidney tissue, and the expression of genes related to inflammation and apoptosis in a rat model of SCI. In this investigation, thirty-five adult male rats were divided into five experimental groups: a control group, a group subjected to spinal cord injury (SCI), a group treated with an alcoholic extract of Melissa officinalis, a group treated with an alcoholic extract of Rosmarinus officinalis, and a group receiving both extracts. The extracts were administered via intraperitoneal injection starting one-day post-SCI and continued for 28 days. Evaluations of sensory and motor functions were performed weekly, while changes in kidney tissue and the expression of genes associated with inflammation and apoptosis were assessed using histomorphometric techniques and quantitative real-time polymerase chain reaction (PCR). The results indicate that the alcoholic Melissa officinalis and Rosmarinus officinalis extracts significantly enhanced sensory and motor functions while reducing the expression levels of genes associated with inflammation (TNF-α) and apoptosis (caspase-3, Bax, and Bcl-2). These findings underscore the potential of these plant extracts in improving the management and treatment of spinal cord injury (SCI) and its secondary effects.

Abstract: Hypoxia-inducible factor-1α (HIF-1α) is a well-known transcriptional regulator that me-diates a broad spectrum of cellular responses to hypoxia, including angiogenesis, extra-cellular matrix remodeling, and metabolic reprogramming. These activities can be achieved by up-regulation of numerous genes, such as vascular endothelial growth fac-tors, fibroblast growth factors, and platelet-derived growth factors, which are involved in the growth regulation of normal tissues and solid tumors. Of note, HIF-1α-mediated regu-lation of the solid tumor’s microenvironment effectively modulates tumor sensitivity to anticancer therapies and thereby can contribute to disease progression. We show here that a 2-aminopyrrole derivative (2-amino-1-benzamido-5-(2-(naphthalene-2-yl)-2-oxoethylidene)-4-oxo-4,5-dihydro-1-H-pyrrole-3-carboxamide – 2-ANPC), previously shown as a potent microtubule-targeting agent, effectively down-regulates HIF-1α expression in a broad spectrum of cancer cell lines, including breast, lung, and prostate cancer. The downregulation of HIF-1α expression in 2-ANPC-treated cancer cells was due to en-hanced proteasome-mediated degradation, whereas the proteasome inhibitor MG-132 ef-fectively reversed this downregulation. 2-ANPC’s potency to down-regulate HIF-1α was also shown in vivo by using the 4T1 breast cancer syngraft model. Important, this 2-aminopyrrole derivative also down-regulated the expression of vascular endothelial growth factor receptors 1 and 3 (VEGFR1 and 3) in 4T1 tumors, which correlated with de-creased tumor weight and size. As expected, an increase of apoptotic (i.e., cleaved caspa-se-3-positive) cells was detected in 4T1 tumors treated with 2-aminopyrrole derivative. Lastly, using various computational tools, we identified four potential binding sites for 2-ANPC to interact with HIF-1α, HIF-1β, and the p300 complex. Collectively, we show here, for the first time, that HIF-1α is a novel molecular target for the 2-aminopyrrole de-rivative (2-ANPC), thereby illustrating it as a potential scaffold for the development of po-tent chemotherapeutic agents with anti-angiogenic activity.

Abstract: Inflammatory Bowel Disease (IBD), which includes Ulcerative Colitis (UC) and Crohn's Disease (CD), is characterized by chronic inflammation and disruption of the intestinal barrier, which is a key pathophysiological mechanism. The efficacy of existing therapies is often inadequate, underscoring the imperative to identify new therapeutic targets. Recently, the concept of PANoptosis has emerged as a critical pathophysiological mechanism in IBD. PANoptosis describes a coordinated form of regulated cell death that incorporates key features of apoptosis, necrosis, and pyroptosis, and is activated through the Panoptosome complex or similar pathways. Targeting central regulators, such as RIPK1 (with agents such as Necrostatin-1), has been shown to protect the intestinal barrier in preclinical models. Furthermore, the combination strategy involving inhibitors of Panapoptotic death (to address the cause of cell death) and established biological agents (e.g., anti-TNF-α) represents the most advanced therapeutic perspective. This review describes the role of Panapoptotic death in the pathogenesis of IBD, current therapeutic strategies targeting Panoptosis, available clinical and preclinical data, molecular tools and pharmaceutical interventions, and future directions that will determine the clinical exploitation of these mechanisms. Finally, Panoptosis is examined not only as a single therapeutic target but also as a platform for the development of combination therapies that lead to more personalized and effective treatment in IBD.

Abstract: The chorioallantoic membrane (CAM) is a well-vascularised extra-embryonic mem-brane that supports avian embryonic development, and can be used as an implantation site for xenograft models of various cancers. CAM tumour research models are powerful and versatile, offering a rapid, cost-effective and ethical complement to mouse xenograft studies. Their capacity for real-time observation of tumour growth, angiogenesis and metastasis within an immunocompetent living organism are particularly compelling. While CAM models have been extensively utilised for investigating solid cancers such as breast, lung and pancreatic, their potential for haematological malignancy research remains comparatively underexplored. This review examines the relevance, advantages and translational potential of avian CAM models in studying blood cancers. Their ap-plications across three primary categories are discussed – leukaemias, lymphomas and myelomas – highlighting experimental approaches that replicate aspects of human disease progression and therapeutic responsiveness. Moreover, the review evaluates species-specific considerations relevant to model fidelity, including evolutionary dis-tance and functional parallels between avian and human haematopoiesis. These com-parisons underscore both the opportunities and limitations for utilising CAM models in haematologic malignancy research. For their potential to investigate mechanisms of cancer development and treatment in simple but immunocompetent in vivo settings, we propose that CAM tumour models offer high value as a bridge between in vitro and mammalian in vivo studies for haematology translational research.

Abstract: Oncofetal reprogramming has recently emerged as a critical concept in translational cancer research, particu-larly for its role in driving therapeutic resistance across a variety of malignancies. This biological process refers to the pattern of gene expression that is restricted to embryogenesis, but becomes expressed again in a sub-population of cancer cells. These genes are typically suppressed after embryogenesis, and their aberrant re-expression in tumors endows cancer cells with stem-like properties and enhanced adaptability. The GOAL of this review is to: i) Comprehensively examine the multifaceted nature of oncofetal reprogramming, ii) Elucidate its underlying molecular mechanisms, including its regulators and effectors, and iii) Evaluate its consequences on therapeutic response in different cancer types. We comprehensively integrate the latest findings from col-orectal, breast, lung, liver, and other cancers to provide a detailed understanding of how oncofetal programs interfere with tumor response to treatment. Among the candidates, YAP1 and AP-1 have emerged as central transcriptional drivers of this reprogramming process, especially in colorectal and breast cancers. We also ex-plore the distinct expression patterns of oncofetal genes across different tumor types and how these patterns correlate with treatment outcomes and patient survival. Lastly, we propose a dual-targeting therapeutic strategy that simultaneously targets both cancer stem cells and oncofetal-reprogrammed populations as more effectively approach to overcome resistance and limit recurrence.

Abstract: Background: Fetal Growth Restriction (FGR) is an important obstetric condition associat-ed with perinatal morbidity and long-term developmental risks. This study aimed to evaluate the genetic etiology of isolated FGR using karyotyping, chromosomal microarray analysis (CMA), and trio-based whole exome sequencing (WES). Methods: A retrospective cohort of 153 fetuses with isolated FGR (diagnosed by ultrasound, from February 2018 to July 2024) underwent karyotyping and CMA. Negative cases (n=50) were further analyzed by trio-WES. Results: Karyotyping identified chromosomal abnormalities in 3 cases (2.0%), while CMA detected pathogenic/likely pathogenic CNVs or UPD in 12 cases (7.8%), in-cluding the 3 with chromosomal abnormalities and 9 cases with normal karyotypes (6.0%), CMA increased diagnostic yield by 5.9%, detecting CNVs/UPD missed by karyo-typing. Trio-WES in 50 cases with normal karyotypes and CMA findings identified 14 pathogenic or likely pathogenic variants in 12 cases (24%), with 7 cases (14%) having var-iants directly related to FGR, including one case of uniparental disomy (UPD) that was missed by CMA. Additionally, WES identified 1 case of FGR caused by maternal hyper-phenylalaninemia and 7 pathogenic variants not directly related to FGR, highlighting the need for comprehensive genetic counseling. These findings underscore the potential of WES to uncover maternal genetic disorders that may impact fetal growth and develop-ment. Conclusions: Integration of CMA and WES into prenatal protocols improved diag-nostic yield in isolated FGR. WES allows the detection of UPD, which can be missed by CMA alone, thus enhancing genetic evaluation of FGR. Moreover, WES has the potential to identify maternal genetic conditions that may affect fetal growth, providing valuable in-sights for genetic counseling and multidisciplinary management.

Abstract: The Universe has two domains: Life and Non-Life, which manifest the dimensionless relativity ratio with basic codes. For life is a/b = a/(1-a) = (1-b)/b (Floating Ratio), and for Non-Life is a/b = (a + b)/a = 1 + b/a (Golden Ratio). Life and Non-Life can be connected and co-exist by the two fractional distribution functions of “1”.The Mass Action Law (MAL) Median Effect Principle leads to the Unified General Dynamics Theory and algorithm, which provides an interdisciplinary and cross-disciplinary common linkage of parameters for computerized digital research and development informatics.

Abstract: Background/Objectives: New approaches using plant-based extracts are increasingly investigated for osteoporosis treatment, including hop extract, which contains potent compounds that affect bone quality favorably. The objective of this research was to evaluate the effect of alendronate, standardized hop extract and their combination on bone tissue quality, hematological and biochemical parameters, and markers of bone turnover in a rat model of osteoporosis. Methods: The study was performed on 6 month-old female Wistar rats. Sham operation was done on 10 animals, and bilateral ovariectomy on 60 animals. Ovariectomized animals were divided into 6 groups, one not treated, and the others treated with a low dose of alendronate, high dose of alendronate, hop extract, or a combination of low/high dose of alendronate and hop extract. Quality of bone was assessed using micro-CT imaging. Hematology and serum biochemistry were analyzed using standardized kits, and bone turnover markers using Western blot. Results: Treatment with high-dose alendronate, hop extract, and a combination of low-dose alendronate and hop extract significantly improved bone quality in ovariectomized animals, but high-dose alendronate combined with hop extract had no favorable effect. Hematological and biochemical parameters were mostly unaffected and within normal range. Changes in markers of bone turnover were modest. Conclusions: For the first time, the effect of combined use of alendronate with hop extract was analyzed. The combination of a low-dose alendronate with hop extract produced effects comparable to those observed with high-dose alendronate or hop extract alone. Standardized hop extract could be a valuable addition to current osteoporosis therapy.

Abstract: The progress, reproducibility, and validity of life sciences research depend on maintaining robust data integrity. The complete need for truthful and transparent data practices highlights the severe implications of data fabrication and falsification, including inaccurate research findings, misguided policy decisions, and reputational damage. Retraction data, statistics and case studies show a marked increase in research misconduct, which now accounts for over 60% of the biomedical sciences retractions, with significant impacts on scientific advancement, resource utilization, and public trust. Strengthening research integrity through improved editorial oversight, post-publication review systems, and further measures is discussed. Data integrity is not just an ethical necessity; it is essential for ensuring reliable research outcomes and preventing the dissemination of misinformation.

Abstract: Short-chain fatty acids (SCFAs), acetate, propionate, and butyrate, are microbial me-tabolites with recognised roles in gut and immune homeostasis, but their therapeutic relevance in gastric cancer, particularly in combination with chemotherapeutics, re-mains unclear. This study investigated the antiproliferative synergy between a com-bined SCFA mixture (APB) and doxorubicin (Dox) in AGS gastric adenocarcinoma cells using integrated cellular, molecular, and proteomic approaches. APB and Dox each inhibited cell proliferation, with IC₅₀ values of 568.33 ± 82.56 μg/mL and 0.22 ± 0.04 μg/mL, respectively, and their combination (3000 + 0.27 μg/mL) enhanced cyto-toxicity, achieving 103.46% inhibition and reducing the APB IC₅₀ to 512.80 ± 18.37 μg/mL. Combination Index values confirmed synergistic interactions (CI₅₀ = 0.61; CI₉₅ = 0.13). APB+Dox significantly increased apoptosis (94.83%) with minimal necrosis (4.64%) and induced strong ROS generation comparable to APB alone, while Dox showed limited oxidative effects. Proteomic profiling revealed downregulation of ri-bosomal proteins and cell cycle regulators in Dox and APB+Dox groups, with the com-bination further enhancing apoptosis-related pathways and stress responses. Overall, these findings indicate that SCFA-based interventions, exemplified by APB+Dox, may offer a low-toxicity strategy to potentiate chemotherapy efficacy in gastric cancer through apoptosis induction, redox disruption, and attenuation of drug resistance.

Abstract: Cancer progression and metastasis are associated with disrupted intercellular communication and metabolic reprogramming. Extracellular vesicles (EVs) and non-vesicular nanoparticles (NVNPs), particularly those enriched in lipids, play essential roles in mediating signaling pathways that promote tumor growth, immune evasion, and resistance to therapy. This article describes recent findings on lipid-mediated intercellular communication, with a focus on the lipid composition of EVs and NVNPs, and their involvement in shaping the tumor microenvironment, guiding organotropism, and establishing pre-metastatic niches. Additionally, explore the reverse-microevolution perspective on cancer and investigate the ancestral functions of lipid-based vesicular systems. Biogenesis and intracellular trafficking of exomeres and supermeres are also discussed in this article. Emerging evidence indicates that exploiting the biological properties of these particles could pave the way for novel therapeutic strategies targeting lipid-driven oncogenic pathways. A deeper understanding of these mechanisms is essential for intercepting cancer progression at its earliest stages.

Abstract:

The intensive use of pesticides in agriculture poses serious risks to aquatic ecosystems and non-target organisms, yet toxicological data remain limited. This study evaluated the acute effects of three widely used pesticides—pirimiphos-methyl (10 and 60 μg/L), propamocarb hydrochloride (40 and 80 μg/L), and 2,4-D (50 and 100 μg/L)—on the liver of common carp (Cyprinus carpio Linnaeus, 1758), a sentinel species in aquaculture, but also a species equally important in risk assessment and environmental monitoring. Fish were exposed for 96 hours under controlled conditions, and histopathological, histochemical, and biochemical biomarkers were analyzed. All tested pesticides induced significant histopathological alterations, predominantly circulatory and degenerative changes, with severity increasing at higher concentrations. Propamocarb hydrochloride and 2,4-D caused more pronounced and partly irreversible hepatotoxicity compared to pirimiphos-methyl. Histochemical assessment revealed altered glycogen metabolism, while biochemical assays showed inhibition of key liver enzymes, such as ALAT and ASAT, but also ChE and LDH, indicating disrupted metabolic processes. These findings highlight the vulnerability of aquatic organisms to pesticide exposure and support the use of fish liver biomarkers as effective tools in ecotoxicology research. The study also emphasizes the need for stricter regulation and environmental monitoring of pesticide contamination in aquatic systems.

Abstract:

Background: Melatonin, an indolic neuromodulator with oncostatic and anti-inflammatory properties, is produced at extrapineal sites—most notably in the gut. Its canonical actions are mediated by high-affinity GPCRs (MT1/MT2) and by the melatonin-binding enzyme NQO2 (historically “MT3”). A growing body of work highlights a bidirectional interaction between the gut microbiota and host melatonin. Methods: We integrate two lines of work: (i) three clinical cohorts—cardiac arrhythmias (n = 111; 46–75 y), epilepsy (n = 77; 20–59 y), and stage III–IV solid cancers (25–79 y)—profiled with stool 16S rRNA sequencing, SCFA measurements, and circulating melatonin/urinary 6-sulfatoxymelatonin; and (ii) an age-spanning cognitive cohort with melatonin phenotyping, microbiome analyses, and exploratory immune/metabolite readouts, including a novel observation of melatonin binding on bacterial membranes. Results: Across all three disease cohorts we observed moderate-to-severe dysbiosis with reduced alpha-diversity and shifted beta-structure. The core dysbiosis implicated tryptophan-active taxa (Bacteroides/Clostridiales proteolysis and indolic conversions) and depletion of SCFA-forward commensals (e.g., Faecalibacterium, Blautia, Akkermansia, several Lactobacillus/Bifidobacterium spp.). Synthesized literature indicates that typical human gut commensals rarely secrete measurable melatonin in vitro; rather, their metabolites (SCFAs, lactate, tryptophan derivatives) regulate host enterochromaffin serotonin/melatonin production. In arrhythmia models, dysbiosis, bile-acid remodeling, and autonomic/inflammatory tone align with melatonin-sensitive antiarrhythmic effects. Epilepsy exhibits circadian seizure patterns and tryptophan-metabolite signatures, with modest and heterogeneous responses to add-on melatonin. Cancer cohorts show broader dysbiosis consistent with melatonin’s oncostatic actions. In the cognitive cohort, the absence of dysbiosis tracked with preserved learning across ages; exploratory immunohistochemistry suggested melatonin-binding sites on bacterial membranes in ~15–17% of samples. Conclusions: A unifying microbiota–tryptophan–melatonin axis plausibly integrates circadian, electrophysiologic, and immune–oncologic phenotypes. Practical levers include fiber-rich diets (to drive SCFAs), light hygiene, and time-aware therapy, with indication-specific use of melatonin.

Abstract: Tumor rupture is a rare complication of uterine leiomyosarcoma. We report a case of ruptured uterine leiomyosarcoma containing ectopic components, diagnosed after the onset of abdominal pain following endoscopic examination of the lower gastrointestinal tract. The patient was a 56-year-old woman who had been diagnosed with anemia at 48 years of age when she was first referred to our medical team. Contrast-enhanced magnetic resonance imaging (MRI) revealed a 48 mm x 50 mm mass in the anterior wall of the uterine body, which was diagnosed as a uterine fibroid. After 8 years of regular follow-up once or twice a year, the patient developed abdominal pain after undergoing lower gastrointestinal endoscopy, prompted by a positive fecal occult blood test. Contrast-enhanced computed tomography (CT) showed that the uterine mass had enlarged to 90 mm x 69 mm. T2-weighted contrast-enhanced MRI demonstrated moderate signal intensity and restricted diffusion, and contrast-enhanced T1-weighted MRI revealed high signal intensity suggestive of hemorrhage. The outline of the tumor and uterus was interrupted cephalad to the lesion, raising suspicion of rupture of a malignant uterine mesenchymal tumor. Therefore, total hysterectomy, bilateral salpingo-oophorectomy, and partial omentectomy were performed. Intraoperatively, tumor rupture and adhesion of the ruptured tissue to the ileum were observed, necessitating partial ileectomy. Pathological examination of the resected specimen revealed irregularly proliferating spindle cells with marked nuclear atypia, 12 mitotic figures per 10 High-power fields, coagulative necrosis, and infiltration of multinucleated giant cells. Another notable finding was the presence of ectopic osteosarcoma and chondrosarcoma components.

Abstract:

Recently, GnRHa puberty blockers have been under scrutiny, with newly identified risks of heart and brain damage and recurrent concerns about fertility, cancer risk, and bone health. This study explores the effects of GnRHa on liver morphology, function, and injury response. Peripubertal male and female Sprague-Dawley rats received daily GnRHa triptorelin (100 μg) subcutaneously. Liver oxidative stress, inflammation, and fibrosis were evaluated via malondialdehyde and 8-OHdG (oxidative damage), immunohistochemistry for CK19 (cholangiocytes) and CD45 (leukocytes), and collagen staining as well as áSMA (liver fibrogenesis) and TIMP1 (extracellular matrix breakdown) expression, respectively. Following GnRHa treatment, only male rats exhibited increased ductular reaction and oxidative stress. In contrast, GnRHa-treated female rats showed increased leukocyte infiltration. In both sexes, GnRHa-treated rats showed increased fibrosis, with significantly increased collagen deposition and áSMA expression. Interestingly, GnRHa-treated female rats exhibited increased TIMP1 expression, whereas male rats showed decreased TIMP1 expression. Overall, GnRHa puberty blocking leads to significantly increased liver injury in both sexes. Specifically, biological females are at increased risk of hepatic inflammation, while biological males are at increased risk of oxidative stress. Human clinical trials are crucial for further exploring these findings.

Abstract: This work investigates crowd dynamics in evacuation scenarios by incorporating the effects of emotional contagion. We develop a hybrid modeling framework that couples a mesoscopic kinetic approach for pedestrian motion with an agent-based model describing emotional interactions. Each individual adapts their emotional state based on the average emotion of nearby agents, which in turn affects their walking direction and speed. Numerical simulations, conducted using a Monte Carlo particle method for the kinetic motion model together with an agent-based scheme for emotional contagion, examine three representative scenarios: calm crowds without contagion, fully emotional crowds, and mixed populations. The results show that emotional contagion intensifies congestion and significantly increases evacuation times. The proposed dual-scale model provides a first step toward a comprehensive representation of panic dynamics, offering new insights into the interplay between motion and emotion, with potential applications to crisis management and safety design.