War exposure and displacement increase the risk of posttraumatic stress disorder in children and may coincide with alterations in stress biology, inflammation, growth, and family functioning, with Syrian populations disproportionately affected. We conducted a targeted review informed by the SAMS 2025 poster bibliography with supplementary searches of PubMed/PMC and Google Scholar (2010-2025). Eligible studies included conflict-affected children/adolescents (0-18 years) with PTSD measures and at least one biological or developmental outcome. Two reviewers screened and extracted data and appraised study quality using JBI/NOS-aligned domains. Evidence included school-based samples within Syria and Syrian refugee cohorts in host countries, alongside mechanistic reviews. Findings showed higher cortisol/HPA-axis activity reported in trauma-exposed pediatric samples, and Syrian refugee studies using hair cortisol suggest associations between war exposure and PTSD symptoms. Mechanistic literature suggests possible elevations in inflammatory markers (e.g., IL-6, CRP) in some contexts, but conflict-specific pediatric biomarker data remain limited. Growth impacts are plausibly mediated by cumulative adversity and nutrition insecurity, with sparse direct Syrian cohort evidence. Syrian conflict-affected children experience a substantial mental health burden, and available data suggest biological embedding of trauma via stress and immune pathways; however, most studies are observational and confounding limits causal inference. Epigenetic and intergenerational findings should be interpreted as preliminary and hypothesis-generating. Future longitudinal studies with standardized measures and careful confounding control are needed.
The low cost, and pro-apoptotic property of gold nanoparticles (AuNPs) make them an attractive candidate for the investigation in cancer therapy. Despite promising advances made in cancer research using AuNPs, the molecular mechanisms involved in AuNPs-induced cell death is still remaining largely unknown. This study was undertaken to elucidate the anticancer property of AuNPs by determining the involvement of AuNPs-induced reactive oxygen species (ROS) in the stimulation of autophagy in MCF-7 human breast cancer cells. In this experimental study MCF-7 cells were cultivated in 6-well plates in the presence or absence of AuNPs for 24 h. In addition, to confirm the pivotal role of AuNPs in ROS generation, AuNPs-treated cells were also cultured in the presence of N-acetylcysteine (NAC; as an antioxidant agent) and hydroxychloroquine (HCQ; as an inhibitor of autophagosome formation). Then, the ROS contents of the cells were determined and the effects of AuNPs in the formation of autophagosome and induction of apoptosis were investigated. Also, the relative expression levels of Bax, Bcl2, MAPK P38, JNK, Beclin-1, and LC3 mRNA were analyzed by RT-qPCR and the protein contents of LC3-I/II and Beclin-1 were measured. AuNPs-induced generation of ROS was prevented by the administration of NAC. AuNPs increased formation of autophagosomes and enhanced the expression of autophagy-related proteins such as LC3 and Beclin-1. Moreover, AuNPs triggered apoptosis, increased the ratio of Bax to Bcl-2 gene expression level, and resulted in the loss of mitochondrial membrane potential. In AuNPs-treated cells, the involvement of ROS in boosting autophagy process and increasing apoptosis was confirmed by the ROS-scavenging effects of NAC which successfully suppressed ROS level and prevented autophagy and apoptosis. Our finding suggest that AuNPs-induced ROS can promote autophagy and apoptosis via mitochondrial dysfunction and regulation of the ROS/JNK signaling pathway in MCF-7 cancer cells. Thereby highlighting the potential therapeutic value of AuNPs as anticancer agents.
caffeic acid phenethyl ester (CAPE) and vitamin D inhibit melanoma growth through various anti-tumor mechanisms. The study investigated the impact of a 1:1 molar ratio of CAPE/vitamin D, both in free and liposomal forms, on inducing cytotoxicity in A375 and B16F10 melanoma cell lines, as well as HDF-1 normal human dermal fibroblasts. The physical characteristics of liposomal CAPE/vitamin D prepared by thin-film hydration were analyzed. The cytotoxicity of CAPE and vitamin D combination, in free and liposomal forms, was assessed using the MTT assay, along with their synergy or antagonism analysis. CalcuSyn software was used to calculate the combination index, and the impact of both free and liposomal forms of CAPE/vitamin D on apoptosis and necrosis was examined. Nanomechanical properties and PI3K/AKT1 and BAX/BCL2 gene expression levels were also assessed. The highest drug release from nanoliposomes was recorded at 88.12% for CAPE and 76.39% for vitamin D in pH = 5.5. The encapsulation efficiency of CAPE and vitamin D within liposomes was found to be 81.04% and 72.35%, respectively. The IC50 values for A375, B16F10 and HDF-1 cells exposed to liposomal formulations were 8.74 µg/mL, 13.36 µg/mL and 32.49 µg/mL, respectively, after 48 h, while cells incubated with a free mixture of CAPE and vitamin D had IC50 values of 18.31 µg/mL, 24.53 µg/mL and 40.68 µg/mL, respectively. Liposomal CAPE/vitamin D induced more apoptosis in cells than the free mixture, caused nanomechanical changes, and reduced the expression ratio of PI3K to AKT1 genes. Liposomes containing CAPE and vitamin D in a 1:1 molar ratio were more effective in inducing A375, B16F10 and HDF-1 cells death compared to their free mixture.
Diabetes impairs hearing through microvascular damage and neuropathy, yet the prevalence of moderate-to-severe hearing loss (≥ 40 dB HL) remains inadequately explored. Variations by age, diabetes duration, and socioeconomic factors are inadequately characterised. This systematic review quantified the prevalence and comparative risk of moderate-to-severe hearing loss in diabetes and prediabetes, exploring variations across age, national income level, and disease duration. We searched PubMed, Scopus, Web of Science, SPORTDiscus, and CINAHL (2000-2025) for observational studies reporting audiometric thresholds in diabetic or prediabetic subjects (PROSPERO: CRD42018100742). Quality was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analyses generated pooled prevalence and odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias was evaluated via funnel plots and Egger's regression. Of 3490 records, 29 studies qualified. Most examined type 2 diabetes; one included prediabetes. Twenty-three studies (n = 5221) yielded a pooled prevalence of 24% (95% CI: 19%-30%; I2 = 94%). Eleven studies showed diabetes doubled hearing loss odds versus controls (OR = 2.41, 95% CI: 1.62-3.60; I2 = 86.6%). Risk was significantly elevated in younger adults (< 60 years: OR = 3.03, 95% CI: 2.17-4.22) but not in older adults (≥ 60 years: OR = 1.52, 95% CI: 0.72-3.22). Low- and middle-income countries showed the highest risk (OR = 4.51, 95% CI: 2.43-8.40) versus high-income countries (OR = 1.78, 95% CI: 1.05-3.02). Diabetes duration < 10 years conferred elevated risk (OR = 2.68). Small-study effects were detected (Egger's p = 0.019) but sensitivity analyses confirmed robustness. One in four diabetic adults has clinically significant hearing loss, particularly in younger individuals and resource-limited populations. These findings support the integration of routine audiometric screening into diabetes care.
In our case report, we highlight how mycoplasma presents as a spectrum, ranging from the most benign to the most severe presentations. We report a rare case of a 3-year-old boy with Mycoplasma pneumoniae infection who presented with urticaria multiforme and bicytopenia. It also points out the wide range of possible clinical manifestations of M. pneumoniae in pediatric patients. The report also summarizes a review of the only two published pediatric cases that presented with pancytopenia in the English literature.
Surgical site infections (SSIs) remain a major postoperative complication, particularly among diabetic patients who are inherently at higher risk due to impaired immunity and delayed wound healing. To assess the risk factors associated with SSIs in diabetic patients undergoing elective surgical procedures. This retrospective study was conducted at Children Hospital Lahore, from April 2024 to April 2025. A total of 150 diabetic patients scheduled for elective surgery were enrolled using non-probability consecutive sampling. Preoperative, intraoperative, and postoperative variables were recorded, including glycemic indicators, comorbidities, operative duration, wound classification, antibiotic timing, and postoperative wound status. The mean age of participants was 57.8 ± 11.4 years, and 58.7% were male. The overall SSI rate was 25.3% (n = 38). Higher HbA1c levels were significantly associated with SSI (8.4 ± 1.3 vs. 7.1 ± 1.0, p < 0.001). Operative duration of two or more hours (p = 0.02), contaminated wound classification (p = 0.01), smoking (p = 0.03), and incorrect antibiotic prophylaxis timing (p = 0.04) were also significantly correlated with infection. Logistic regression identified poor glycemic control (adjusted odds ratio (AOR) 3.1, 95% CI: 1.6-5.9), prolonged surgery (AOR 2.4, 95% CI: 1.1-4.8), contaminated wound class (AOR 2.9, 95% CI: 1.3-6.5), and smoking (AOR 1.9, 95% CI: 1.01-3.8) as independent predictors of SSI. Patients who developed SSI had significantly longer hospital stays (9.8 ± 3.1 vs. 5.3 ± 1.9 days, p < 0.001). It is concluded that SSIs in diabetic patients are strongly linked to modifiable perioperative factors. Poor glycemic control, prolonged operative duration, contaminated wounds, and smoking significantly increase infection risk.
Urogenital tuberculosis is difficult to diagnose in the general healthcare network because it has no pathognomonic symptoms, and there is no screening for urogenital tuberculosis, which complicates its timely diagnosis. This article presents a clinical case of generalized tuberculosis that first manifested as a lesion of the external genital organs. A high level of clinical suspicion for tuberculosis prompted special investigations using widely available methods. Real-time PCR diagnostics allowed to identify tuberculosis of the male genital organs as the first manifestation of generalized tuberculosis. We present a rare case of urogenital tuberculosis diagnosed by ejaculate analysis, as well as a successful treatment outcome. The key factor in timely diagnosis of tuberculosis is physician awareness, which is based on a certain minimum level of knowledge about the infection.
The glycopeptide antibiotic colistin (polymyxin E) causes dose-dependent nephrotoxicity. The pathophysiology of colistin-induced nephrotoxicity involves processes such as ischemia, inflammation, and apoptosis. By alleviating oxidative stress, inflammation, and apoptosis, crocin, a key component of Crocus sativus protects the kidneys from toxicity. This study designed to explore the protective effects of crocin against colistin-induced cytotoxicity in HEK-293 cells. HEK-293 cells were treated with varying concentrations of crocin (1.25 - 40 μM) for 24 hr before exposure to 160 µM colistin (the IC50 value). Cell viability was measured using an MTT assay. Intracellular reactive oxygen species (ROS) levels were measured using DCFH, and Western blotting was performed to analyze the expression of Bcl-2, Bax, and caspase-3 proteins. Pre-treatment with crocin at concentrations of 1.25 (p<0.001), 2.5, and 5 (p<0.01) µM effectively enhanced cell viability, which had been diminished by colistin. Furthermore, crocin mitigated the elevated levels of ROS induced by colistin (p<0.001). The findings reveal that crocin prevented the upregulation of pro-apoptotic proteins Bax (p<0.05) and caspase-3 (p<0.01), and countered the downregulation of the anti-apoptotic protein Bcl-2 (p<0.05) triggered by colistin in HEK-293 cells. Crocin serves as a natural compound that alleviates colistin-induced cytotoxicity through inhibiting oxidative stress and preventing apoptosis induction. As a result, crocin stands out as a promising antioxidant for preventing colistin-induced cytotoxicity, especially in renal cells.
Sanjad-Sakati Syndrome (SSS) is a rare autosomal recessive disorder characterized by congenital hypoparathyroidism, dysmorphic features, and severe growth failure. This study aims to examine the clinical picture, comorbidities, and mortality rate of SSS in Jordan. This retrospective study included all patients diagnosed with SSS at the pediatric endocrinology clinics of Queen Rania Al Abdullah Hospital for Children, Amman, Jordan, between January 2002 and August 2025. Twenty-two children were evaluated for demographic characteristics, growth parameters, biochemical findings, comorbidities, and mortality rate. Of the 22 patients (age range: 4 months-23 years), 14 were male and 8 were female. All patients presented with low birth weight, dysmorphic features, hypocalcemia, congenital hypoparathyroidism, and short stature. Parental consanguinity was recorded in 88.8% of the families. Nephrocalcinosis occurred in 31.8% of the patients ( n  = 7), chronic intestinal pseudo-obstruction in 22.7% ( n  = 5), and subclinical hypothyroidism in 9.1% ( n  = 2). Ten patients (45.5%) died, most commonly due to pneumonia and sepsis. Patients with SSS in Jordan consistently presented with congenital hypoparathyroidism, developmental delay, intellectual disability, and severe growth failure. Frequent comorbidities include nephrocalcinosis, dental anomalies, intestinal pseudo-obstruction, and complications from chronic calcium therapy. These comorbidities are associated with increased mortality rate in SSS.
The tumor microenvironment (TME) is a highly adaptive and heterogeneous niche in which cancer stem cells (CSCs) promote immune evasion, metastatic dissemination, and therapy resistance. Among the mechanisms that support this phenotype, mitochondrial hijacking has emerged as a central strategy through which CSCs reprogram immune and stromal cells to favor tumor progression. This review synthesizes current evidence on how CSCs exploit mitochondrial transfer, particularly via tunneling nanotubes (TNTs) and extracellular vesicles (EVs), to impair antitumor immunity and remodel the metastatic niche. CSCs display marked metabolic plasticity, shifting between glycolysis and oxidative phosphorylation (OXPHOS) in response to environmental stress. They exploit this adaptability by transferring mitochondria and mitochondrial components to recipient cells, including tumor-associated macrophages (TAMs) and cytotoxic T cells, thereby disrupting ATP production, increasing oxidative stress, and skewing immune polarization. This mitochondrial hijacking contributes to an immunosuppressive milieu, stabilizes HIF-1α, and enhances PD-L1 expression, ultimately weakening T-cell activity and reinforcing CSC survival. EVs add another layer of regulation by transporting bioactive cargo, including oncogenic microRNAs (miRNAs) and mitomiRs such as miR-21, miR-210, and miR-34a. These molecules modulate mitochondrial gene expression, reshape immune signaling, and reinforce CSC phenotypes through autocrine and paracrine loops. Single-cell and spatial transcriptomic approaches have further revealed metabolic heterogeneity within CSC-immune synapses, identifying "metabolic hotspots" associated with profound immune dysfunction. Therapeutic strategies targeting OXPHOS, EV biogenesis, and miRNA activity are therefore being explored. In parallel, mitochondria-associated proteins such as TSGA10 may also contribute to CSC-driven immunometabolism regulation and deserve further investigation. Targeting downstream heterogeneity is like cutting the branches of a weed. Targeting the upstream mechanisms of mitochondrial hijacking and miRNA crosstalk aims to destroy the root (CSC plasticity) that generates the heterogeneity and drives therapy resistance in the first place. This review highlights mitochondrial hijacking and miRNA-mediated reprogramming as central determinants of CSC-driven immune escape and proposes a framework for precision interventions targeting CSC-immune interactions in metastatic cancer.
Stroke is a devastating medical condition, and one of its side effects is post-stroke cognitive impairment (PSCI). The objective of this study is to investigate and analyse the potential indicators for post-stroke cognitive decline (PSCI), with a particular emphasis on the biomarkers Aβ42 (beta-amyloid 42) and haemoglobin (Hb) levels. Based on clinical diagnosis, 120 participants were divided into three groups: PSCI (n = 40), PSCN (n = 40), and AD (n = 40): Alzheimer's disease (AD), post-stroke cognitive impairment (PSCI), and post-stroke cognitively normal (PSCN). The first data set was documented. The study examined the relationship between Aβ42 and Hb and cognitive score. Finally, ROC curve and logistic regression analysis were used to analyze the aforementioned indicators' PSCI prediction abilities. Compared to the AD group (104.00 ± 64.43 pg/ml, 112.4 ± 19.05 g/L) and the PSCN group (87.38 ± 66.69 pg/ml, 134.8 ± 13.28 g/L), the PSCI group had lower levels of Aβ42 (69.20 ± 49.36 pg/ml) and Hb (110.53 ± 22.73 g/L) (P < 0.05). The study identified Hb, age, and hypertension as the main risk factors for PSCI, while Aβ42 was noted as a pertinent risk factor. The sensitivity level was 0.800, specificity was 0.625, and area under the curve for the combination diagnosis of Aβ42 and Hb was 0.7169, according to the ROC curve. The risk variables for PSCI, Aβ42 and Hb, are considerably lower in the blood of patients with PSCI compared to controls. The performance of differential diagnosis will be enhanced when the two are integrated.
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Acute heart failure is a common cause of emergency department admissions and is associated with high morbidity and mortality. To evaluate the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in predicting severity and clinical outcomes in patients presenting with acute heart failure in the emergency department. This cross-sectional analytical study was conducted at the Department of Cardiology, Punjab Institute of Cardiology, Lahore, Pakistan from January 2025 to July 2025, on 225 patients diagnosed with acute heart failure. NT-proBNP levels were measured at admission. Patients were followed during hospital stay for outcomes including severity of heart failure, need for ICU admission, duration of hospital stay, complications, and in-hospital mortality. The mean NT-proBNP level was significantly higher in patients with severe heart failure compared to mild to moderate cases (6,920 ± 2,310 pg/mL vs 3,240 ± 1,580 pg/mL, p < 0.001). Patients requiring ICU admission and those with complications or mortality had markedly elevated NT-proBNP levels (p < 0.001). A significant positive correlation was observed between NT-proBNP levels and duration of hospital stay (r = 0.52, p < 0.001). Receiver operating characteristic curve analysis showed good predictive accuracy for severe acute heart failure, with an area under the curve of 0.86 (95% CI: 0.80-0.91; p<0.001). The optimal NT-proBNP cutoff value of 5000 pg/mL was determined using the Youden Index, yielding a sensitivity of 82.1% and specificity of 76.4%. NT-proBNP is a reliable prognostic marker in acute heart failure, strongly associated with disease severity, adverse outcomes, and prolonged hospitalization. Its use in the emergency department can facilitate early risk stratification and guide clinical decision-making.
Artificial intelligence (AI) is increasingly impacting the cooperation sector, transforming how humanitarians are operating in the field. AI tools now allow for improved health diagnostics and quality services. In conflict areas, organizations are able to improve the efficiency of their analysis, and propose optimized data management processes for more multifactorial predictions. In a context where human and financial resources are limited, AI address the gaps to sustain emergency responses. In this commentary, we explore the trade-offs of adopting those tools and the ethical concerns their usages raise in a fragile environment. Security breach due to human errors and unregulated data management are a substantial risk to the humanitarian workers but also to the communities they aim to protect via their interventions. In this work, we touch upon humanitarians' concerns with this new technology, and reflect on balancing those with the benefits of accuracy of interventions. We argue that the humanitarian sector must not overlook these technologies, as failing to adopt them, risks widening inequalities in access to data-driven decision-making and leaving vulnerable systems further behind. At the same time, it is essential to establish meaningful safeguards and promote local ownership to ensure that AI enhances resilience, rather than reinforcing existing power imbalances.
Genito-Pelvic Pain/Penetration Disorder (GPPPD) is a distressing sexual dysfunction often shaped by psychological and sociocultural factors. Although sexual self-schema and temperament traits may contribute to GPPPD, little is known about their role in non-Western contexts such as Iran. This study aimed to compare sexual self-schema, affective-emotional temperament, and selected sociocultural factors between Iranian women with GPPPD and healthy controls. This case-control study recruited married women aged 18-45 years from a referral fertility and sexual health clinical setting in Tehran, Iran. Cases were clinically diagnosed with GPPPD, and controls were randomly selected from eligible women attending the same settings. Participants completed validated Persian versions of the Sexual Self-Schema Questionnaire and Affective and Emotional Composite Temperament Scale. Demographic and psychosocial data, including self-reported religiosity and employment characteristics, were collected. Multivariable logistic regression identified factors associated with GPPPD. The final sample included 75 women: 38 with GPPPD and 37 controls. Women with GPPPD had higher shy-cautious schema scores than controls (19.5 ± 4.2 vs 17.3 ± 4.2; p = 0.035). Emotional sensitivity was also higher in women with GPPPD (35.7 ± 5.9 vs 33.6 ± 7.9) and independently associated with GPPPD (OR = 1.14, 95% CI: 1.02-1.27). Obsessive temperament was positively associated with GPPPD (OR = 2.54, 95% CI: 1.09-5.89), while euthymic temperament was negatively associated (OR = 0.47, 95% CI: 0.25-0.90). Higher self-reported religiosity increased the odds of GPPPD (OR = 5.89, 95% CI: 1.47-23.69), whereas spousal freelance employment reduced the odds (OR = 0.20, 95% CI: 0.04-0.98). These findings suggest that GPPPD in Iranian women may be better understood within an integrated psychological and sociocultural framework incorporating cognitive schemas, emotional sensitivity, temperament traits, and religious beliefs, supporting culturally sensitive psychological assessment and intervention. Pain or difficulty during sexual intercourse is a common but often misunderstood problem for many women. This study looked at how personality traits and beliefs about sexuality might be linked to a condition called Genito-Pelvic Pain/Penetration Disorder (GPPPD) among married women in Iran. We compared 38 women diagnosed with GPPPD to 37 women without sexual problems. Each participant completed questionnaires that measured emotional traits and sexual self-image. Women with GPPPD were more likely to describe themselves as shy or cautious in sexual situations, more emotionally sensitive, and more likely to have obsessive personality traits. They also reported higher levels of religiosity. In contrast, women with more positive and stable moods were less likely to have GPPPD. These findings suggest that psychological and cultural factors—such as beliefs about sexuality, emotional temperament, and religious values—play important roles in this condition. Understanding these links can help healthcare professionals design more effective, culturally sensitive treatments for women experiencing sexual pain or fear of penetration.
Portal hypertension is a major consequence of chronic liver disease and a key determinant of clinical outcomes, traditionally assessed using the invasive hepatic venous pressure gradient (HVPG). Given the limitations of HVPG measurement, ultrasound-based elastography has emerged as a promising noninvasive alternative. This systematic review evaluated the diagnostic accuracy of liver stiffness measurement (LSM) and spleen stiffness measurement (SSM), obtained through transient elastography (TE) and shear-wave elastography (SWE), for detecting HVPG-defined portal hypertension in adults with chronic liver disease. A comprehensive search of PubMed/MEDLINE, Embase, and the Cochrane Library, from database inception through December 2024, identified eight eligible studies comprising 1,636 patients. Clinically significant portal hypertension was primarily defined as an HVPG of ≥10 mmHg. Across studies, LSM demonstrated moderate-to-high discriminatory performance, with area under the receiver operating characteristic curve (AUROC) values ranging from 0.74 to 0.94, depending on modality and population. SWE generally showed superior performance compared with conventional TE, particularly when standardized reliability criteria were applied. SSM provided complementary hemodynamic information and improved risk stratification in selected cohorts, although it did not consistently outperform LSM alone. Variability in stiffness cutoffs and study design contributed to methodological heterogeneity. Overall, ultrasound-based elastography demonstrates clinically meaningful diagnostic accuracy for identifying portal hypertension and offers a practical, noninvasive approach for risk stratification, particularly in compensated cirrhosis; however, it does not fully replace invasive HVPG measurement.
Lung squamous cell carcinoma (LSCC) rarely metastasizes to the parotid gland, with only a handful of cases reported in the literature. Its clinical and pathological presentations closely mimic those of primary parotid squamous cell carcinoma (PSCC). Differentiating solitary metastasis from metachronous primary squamous cell carcinoma (SCC) in patients with a history of smoking and lung cancer presents a significant diagnostic challenge. A 55-year-old man with a history of heavy smoking presented with a solitary parotid mass two years after curative LSCC resection. Excisional biopsy with histological and immunohistochemical analyses confirmed SCC. Based on (1) a clear history of a primary tumor with a known metastatic propensity, (2) the absence of other primary sites on whole-body imaging, (3) histological features (highly consistent with the primary tumor type and no evidence of squamous metaplasia and dysplasia in the ductal or acinar epithelium), and (4) an immunohistochemical profile that effectively ruled out common primary parotid neoplasms, we retained solitary parotid metastasis as LSCC recurrence. However, definitive comparative molecular profiling, which is crucial for distinguishing recurrence from a second primary tumor, could not be performed because of resource limitations. Beyond the diagnostic challenge, this case highlights the complex intersection between rare metastatic sites and the risk of developing a secondary malignancy. In such scenarios, the decision to proceed with systemic therapy without definitive molecular proof of clonal relatedness depends on a robust convergence of clinical context, consistent imaging, and highly suggestive histopathological and immunohistochemical findings. It is imperative that traditional pathology and advanced molecular studies converge to provide not only a diagnosis but also a precise biological understanding of the disease.
CAR-T cell therapy has shown great success in hematological malignancies. However, this immunotherapeutic strategy faces critical challenges in solid tumors mainly due to the key hurdles brought about by the hostile tumor microenvironment (TME). Effective CAR-T cell therapy in solid tumors is hampered by low tumor infiltration of the administered T cells due to the dense fibrotic nature of the TME and its aberrant vasculature. Also, solid tumors shape a highly immunosuppressive milieu in which the cytotoxic activity and persistence of functional CAR-T cells are abolished. Trefoil factor family (TFF) peptides, especially TFF3, have recently drawn a lot of attention due to their pro-tumor activities. Based on the recent evidence, TFF3 is upregulated in solid tumors where it plays roles in chemotherapy resistance, increased survival, and proliferation of cancer cells, expansion of the immunosuppressive cells and enhanced angiogenesis, which contributes to the aberrant tumor vasculature. In this review, we explore how TFF3 signaling contributes to tumor progression and immune escape, and how its inhibition might reshape the tumor microenvironment (TME) to better support CAR-T cell activity. Mounting evidence suggests that blocking TFF3 could help reduce immunosuppression, restore more normal blood vessel structure, and disrupt the pro-fibrotic and tumor-promoting interactions driven by cancer stem cells (CSCs). At the same time, since TFF3 plays an important role in protecting mucosal tissues and promoting repair after injury, its inhibition needs to be approached carefully. We also discuss strategies to selectively block TFF3 within tumors while minimizing unwanted effects on healthy tissues. Gaining a deeper understanding of how TFF3 contributes to therapy resistance may open up new opportunities to enhance CAR-T cell treatment in solid tumors, either through combination therapies or as a preconditioning step before CAR-T cell infusion.
Infectious encephalopathies often present with nonspecific symptomatology; however, patient history, patterns of brain involvement, and comorbidities and immune status can give clues about the cause of infection. This article describes specific imaging findings and overall imaging patterns characteristic for different types of infections dividing those into bacterial, viral, parasitic and prion disease with clinical correlations. Relevant differential diagnoses and guidance on imaging modalities and protocols to use in working up patients presenting with potential infectious encephalopathies is also provided.
Infertility affects millions of women worldwide, and despite current treatment options, definitive therapies remain limited. Emerging regenerative medicine strategies, particularly stem cell therapy and three-dimensional (3D) bioprinting, offer significant potential to repair and regenerate female reproductive tissues. In this scoping review, 199 studies, including in vitro experiments, animal models, and early-stage clinical investigations, were analyzed to evaluate scientific advancements and translational potential in female reproductive tissue engineering. The focus was on stem cell sources, the development of bioinks, and the applications of 3D bioprinting to reconstruct the endometrium, ovary, cervix, and vagina. Stem cells derived from bone marrow, adipose tissue, and menstrual blood improved ovarian function and endometrial regeneration, with several animal studies reporting successful pregnancies. Concurrently, 3D bioprinting technologies enabled the creation of cell-laden scaffolds with promising potential for tissue reconstruction. Remaining challenges include the development of biocompatible bioinks, formation of functional vascular networks, and accurate recreation of extracellular matrix microenvironments. Most current approaches remain at the preclinical stage; however, the growing body of experimental evidence and early clinical investigations indicate promising translational potential and gradual progress toward future clinical application in female reproductive medicine. Although most advances remain at the preclinical stage, the integration of stem cell therapy and 3D bioprinting demonstrates increasing translational readiness and a clear pathway toward future clinical applications. This review highlights the current progress, existing barriers, and essential research directions for advancing regenerative strategies in female reproductive health.