Flubendiamide provokes oxidative stress, inflammation, miRNAs alteration, and cell cycle deregulation in human prostate epithelial cells: The attenuation impact of synthesized nano-selenium using Trichodermaaureoviride.

Flubendiamide (FBD) is a novel diamide insecticide extensively used with potential human health hazards. This research aimed to examine the effects of FBD on PrEC prostate epithelial cells, including Oxidative stress, pro-inflammatory responses, modifications in the expression of oncogenic and suppressor miRNAs and their target proteins, disruption of the cell cycle, and apoptosis. Additionally, the research investigated the potential alleviative effect of T-SeNPs, which are selenium nanoparticles biosynthesized by Trichoderma aureoviride, against the toxicity induced by FBD. Selenium nanoparticles were herein synthesized by Trichoderma aureoviride. The major capping metabolites in synthesized T-SeNPs were Isochiapin B and Quercetin 7,3',4'-trimethyl ether. T-SeNPs showed a spherical shape and an average size between 57 and 96.6 nm. FBD exposure (12 µM) for 14 days induced oxidative stress and inflammatory responses via overexpression of NF-κB family members. It also distinctly caused upregulation of miR-221, miR-222, and E2F2, escorted by downregulation of miR-17, miR-20a, and P27kip1. FBD encouraged PrEC cells to halt at the G1/S checkpoint. Apoptotic cells were drastically increased in FBD-treated sets. Treatment of T-SeNPs simultaneously with FBD revealed its antioxidant, anti-inflammatory, and antitumor activities in counteracting FBD-induced toxicity. Our findings shed light on the potential FBD toxicity that may account for the neoplastic transformation of epithelial cells in the prostate and the mitigating activity of eco-friendly synthesized T-SeNPs.

Expression profile and functional analysis of miR-301b in patients with breast cancer: A bioinformatics, biochemical, and histopathological study.

BACKGROUND: microRNAs (miRNAs) are crucial regulators of various biological processes and molecular functions. Aberrant miRNA expression has been linked in many studies to neoplastic transformation. Among these miRNAs, dysregulation of miR-301b-5p was associated with different types of cancer including breast cancer. Although many research works have investigated the function of miR-301b in carcinogenesis, few have examined its expression, biological, and clinical implications in breast cancer. METHODS: we examined the expression levels of miR-301b-5p in human cancerous breast tissue compared to normal breast controls using different bioinformatic tools and RT-qPCR analyses. RESULTS: we detected that miR-301b-5p was differentially expressed in cancerous breast tissue when compared to normal controls. MiR-301b-5p was detected to be upregulated in high-grade (Grade 3) and triple-negative breast cancers. A significant strong positive correlation was detected between miR-301b and Ki-67, the commonly used proliferative marker in breast cancer. Bioinformatics analyses using the KM plotter revealed that miR-301b has significant prognostic power in assessing the OS of patients with breast cancer. The study also identified many fundamental biological processes and regulatory pathways associated with the investigated miR-301b-related hub genes. Interestingly, the expression pattern and prognostic significance of PTEN, the top hub gene regulated by miR-301b, highlighted the prognostic significance of PTEN in breast cancer. CONCLUSION: The current study findings suggest the potential use of miR-301b-5p as a possible diagnostic and prognostic biomarker in breast cancer. Moreover, this study emphasized the clinical and biological relevance of miR-301b-5p in breast cancer.

Exploring Novel Treatment Modalities for Type 1 Diabetes Mellitus: Potential and Prospects.

Despite the effectiveness of insulin injections in managing hyperglycemia in type 1 diabetes mellitus (T1DM), they fall short in addressing autoimmunity and regenerating damaged islets. This review aims to explore the potential and prospects of emerging treatment modalities for T1DM, including mesenchymal stem cells (MSCs), MSC-derived exosomes, gene therapy, islet allotransplantation, pancreatic islet cell transplantation, and teplizumab. We review emerging treatment modalities for T1DM, highlighting several promising strategies with varied mechanisms and outcomes. Mesenchymal stem cells demonstrate potential in modulating the immune response and preserving or restoring beta-cell function, although variability in sources and administration routes necessitates further standardization. Similarly, MSC-derived exosomes show promise in promoting beta-cell regeneration and immune regulation, supported by early-stage studies showing improved glucose homeostasis in animal models, albeit with limited clinical data. Gene therapy, utilizing techniques like CRISPR-Cas9, offers targeted correction of genetic defects and immune modulation; however, challenges in precise delivery and ensuring long-term safety persist. Islet allotransplantation and pancreatic islet cell transplantation have achieved some success in restoring insulin independence, yet challenges such as donor scarcity and immunosuppression-related complications remain significant. Teplizumab, an anti-CD3 monoclonal antibody, has demonstrated potential in delaying T1DM onset by modulating immune responses and preserving beta-cell function, with clinical trials indicating prolonged insulin production capability. Despite significant progress, standardization, long-term efficacy, and safety continue to pose challenges across these modalities. Conclusion: While these therapies demonstrate significant potential, challenges persist. Future research should prioritize optimizing these treatments and validating them through extensive clinical trials to enhance T1DM management and improve patient outcomes.

Molecular Basis of Hydatidiform Moles-A Systematic Review.

Gestational trophoblastic diseases (GTDs) encompass a spectrum of conditions characterized by abnormal trophoblastic cell growth, ranging from benign molar pregnancies to malignant trophoblastic neoplasms. This systematic review explores the molecular underpinnings of GTDs, focusing on genetic and epigenetic factors that influence disease progression and clinical outcomes. Based on 71 studies identified through systematic search and selection criteria, key findings include dysregulations in tumor suppressor genes such as p53, aberrant apoptotic pathways involving BCL-2 (B-cell lymphoma), and altered expression of growth factor receptors and microRNAs (micro-ribose nucleic acid). These molecular alterations not only differentiate molar pregnancies from normal placental development but also contribute to their clinical behavior, from benign moles to potentially malignant forms. The review synthesizes insights from immunohistochemical studies and molecular analyses to provide a comprehensive understanding of GTD pathogenesis and implications for personalized care strategies.

Is Endoscopy Mandatory In Cases Mimicking Acute Pancreatitis?

Objectives: To detect the utility of nonspecific rising of pancreatic enzymes in patients with stomach discomfort, and to explore the possibility of hyperamylasemia as a differential diagnosis. Method: The cross-sectional study was conducted from April 2020 to April 2021 at two large tertiary care centres in Kafrelsheikh and Zagazig governorates in northern Egypt, and comprised patients complaining of dull aching abdominal pain. They were classified into two groups. Patients with nonspecific rise in pancreatic enzymes less than threefold in the absence of acute pancreatitis were in group I, while those having abdominal pain without rise in pancreatic enzymes were in group II. All patients were subjected to detailed history and clinical examination followed by laboratory assessment, imaging studies and upper endoscopy. Data was analysed using SPSS 20. RESULTS: Of the 270 patients, 170(63%) were in group I; 120(70.5%) males and 50(29.5%) females with mean age 51±6.58 years, There were 100(37%) patientsin group II; 65(65%) males and 35(35%) females with mean age 53±8.96 years (p>0.05). Amylase, lipase, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, Creactive protein and helicobacter pylori values were significantly different between the groups (p<0.05). CONCLUSIONS: Elevation of pancreatic enzymes with a level less than three-fold in patients with abdominal pain reflected mucosal injury of the gastrointestinal tract and may raise the necessity for diagnostic upper endoscopy.

Osteological Study of the Parietal Foramen in the Adult Human Skull Bones and its Clinical and Surgical Correlations / Estudio Osteológico del Foramen Parietal en los Huesos del Cráneo Humano Adulto y sus Correlaciones Clínicas y Quirúrgicas

SUMMARY: Parietal emissary foramina (PEF) are small holes, which are localized between the middle and posterior thirds of the parietal bone posterior surface close to the sagittal suture. PEF are important structures that protect the parietal emissary vein, which passes through it. During neurosurgery procedures, parietal foramina (PF) knowledge is crucial. This work aimed to evaluate presence and location of the PF in the skull of an adult human. Moreover, measure the distance amidst PF and the sagittal suture's midline to ascertain its clinical repercussions. 74 adult human skulls, without gross pathology, were observed for the PF's existence. The PF's and sagittal suture's midline distance were measured. According to the PF patterns of presence, five groups were distributed. Finally, specimens were photographed and subjected to statistical analysis. The PF was absent in 7 skulls (9.5 %). There were 9 skulls (12.2 %) exhibited central parietal foramen where the parietal foramen lies on the sagittal suture. 17 skulls (23 %) showed right unilateral parietal foramen, whereas 15 skulls (20.3 %) demonstrated left unilateral parietal foramen. The final 26 skulls (35.1 %) exhibited bilateral parietal foramen. This descriptive study supplies valuable information of PF variations, which is crucial for neurosurgeons in modifying surgical techniques and procedures to alleviate injury to PF-emerging structures such as emissary veins.

Los forámenes emisarios parietales (FEP) son pequeños orificios que se localizan entre los tercios medio y posterior de la superficie posterior del hueso parietal, cerca de la sutura sagital. Los FEP son estructuras importantes que protegen la vena emisaria parietal, que lo atraviesa. Durante los procedimientos de neurocirugía, el conocimiento de los forámenes parietales (FP) es crucial. Este trabajo tuvo como objetivo evaluar la presencia y ubicación del FP en el cráneo de hombres adultos, además, medir la distancia entre el FP y la línea mediana de la sutura sagital para conocer su repercusión clínica. Se examinaron 74 cráneos humanos adultos, sin patología grave, para determinar la existencia del FP. Se midió la distancia de la línea mediana de la sutura sagital y del FP. De acuerdo con los patrones de presencia del FP, se distribuyeron en cinco grupos. Finalmente, los especímenes fueron fotografiados y sometidos a análisis estadístico. El PF estaba ausente en 7 cráneos (9,5 %). Hubo 9 cráneos (12,2 %) que presentaban un PF central localizándose en la sutura sagital. 17 cráneos (23 %) presentaban un FP unilateral derecho, mientras que 15 cráneos (20,3 %) se observó un FP unilateral izquierdo. Los 26 cráneos restantes (35,1 %) exhibieron FP bilaterales. Este estudio descriptivo proporciona información valiosa sobre las variaciones del FP, que es fundamental para los neurocirujanos en el momento de modificar las técnicas y los procedimientos quirúrgicos para aliviar las lesiones de las estructuras emergentes del FP, como las venas emisarias.

Silymarin attenuates escitalopram (cipralex) induced pancreatic injury in adult male albino rats: a biochemical, histological, and immunohistochemical approach.

Depression is a prevalent global problem since ages, predominately treated with SSRI. Cipralex, is an antidepressant of the SSRIs class used as a remedy for mood, depression and anxiety. Silymarin (SIL), a natural free radical scavenging, has an antioxidant and anti-inflammatory properties. This hypothesis evaluates, for the first time, the role of cipralex on the structure of the endocrine and exocrine components of the pancreas and assess the beneficial effects of SIL on these changes. Forty-five rats were divided into control, cipralex, and cipralex plus SIL groups. During sacrifice, all rats and pancreases were weighed and the ratio of pancreatic weight (PW) to rat weight (RW) was calculated, blood samples were collected to estimate fasting glucose, insulin and amylase levels, the specimens were prepared for histological, immunohistochemical (inducible nitric oxide synthase [iNOS], tumour necrosis factor-alpha [TNF-α], caspase 3, proliferating cell nuclear antigen [PCNA], and anti-insulin antibody), and morphometrical studies. Cipralex group exhibited marked destruction of the pancreatic architecture of the exocrine and endocrine parts, with a dense collagen fiber deposition. Also, there is highly significant decrease (P<0.001) of PW/RT ratio, insulin, and amylase levels, the number and diameter of islets of Langerhans, the number of PCNA positive immunoreactive cells, and the number of insulin positive ß-cells. Furthermore, a highly significant increase of glucose level, iNOS, TNF-α, and caspase-3 positive immunoreactive cells in the islets of Langerhans and acinar cells were observed. SIL improves the pancreatic histological architecture, weight loss, biochemical, and immunohistochemical analyses. Administering SIL is advantageous in managing cipralex induced pancreatic injury via its anti-inflammatory, antioxidant, and anti-apoptotic qualities.

Can fecal calprotectin reflect your colonic status?

Background: Organic colonic manifestation may be difficult to be differentiated from functional one. Inflammatory bowel disease (IBD) is a common chronic inflammatory and destructive disease of the bowel wall. Chronic inflammation is associated with ulcerations, strictures, perforations, and it is a risk factor for dysplasia and cancer. To reduce these long-standing complications, IBD patients are in a continuous need for early diagnosis1. Markers, such as erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP), fecal calprotectin (FC) have been widely used as noninvasive parameters for IBD monitoring. We aimed, in this current study, to evaluate the value of fecal calprotectin and other noninvasive biomarkers in predicting abnormal histologic findings in patients undergoing colonoscopy.in addition to determine the cutoff value which predict IBD2. Methods: The present prospective study included 160 patients with complaint of colicky abdominal pain with frequent diarrhea associated with mucous and infrequent bleeding per rectum for more than 6 months. They presented partial improvement with medication and recurrence once stopping the treatment These patients had been recently diagnosed with IBD at many primary healthcare centers covering the areas of the Kafrelsheikh and Zagazik governorate in the North of Egyptian Nile delta. After complete history, clinical examination, and laboratory investigation, they were referred to the IBD clinic at Kafrelsheikh University Hospital for assessment and ileocolonoscopy with biopsies. Results: There was a wide spectrum of age of the studied patients, with mean age 40.12±7.88 (minimum 18 and maximum 56 years). Regarding gender, males represented 87.5% of the studied patients. Forty percent of the patients with colonic manifestation were smokers, 57% preferred a spicy diet, and the majority had low educational level (77.5%). Forty percent had obvious blood in stool, 55% had occult blood, and raised ESR CRP occurred in 32.5% and 50%, respectively. Fecal calprotectin cutoff was>159, with sensitivity 92.8% and specificity 97.5%. Conclusions: Biomarkers (FC, ESR, CRP) can be used as noninvasive parameters for the early diagnosis and prediction of organic colonic disease. Fecal calprotectin in the IBD group revealed significant area under the curve (AUC) values and cutoff> 159, with sensitivity 92.8% and specificity 97.5%. (AU)

The Relationship between the Connexin 32 and Connexin 43 Genes and the Pretreatment Stage and Short-term Follow-up of Patients with Acute Myeloid Leukemia.

Background: Connexins (Cxs) are gap junction proteins involved in the communication between acute myeloid leukemia (AML) and stromal cells. They consist of intercellular channels termed "connexions", which can cause uncontrolled cell proliferation if dysregulated. This study aimed to evaluate the expression levels of the Cx32 and Cx43 genes and their correlations with other prognostic markers in patients with AML. Methods: This cross sectional study was performed on peripheral blood samples from 60 newly diagnosed patients with AML and 40 healthy control subjects at Kasr Alainy School of Medicine, Cairo University, from June 2016 to December 2017. The quantitative real-time polymerase chain reaction (qRT-PCR) test was used to examine the relative expression level of Cx43 and Cx32 genes in the patients and the control subjects. The Chi square test or the Fisher exact test was employed to examine the relationship between qualitative variables, while the independent t test or the Mann-Whitney test was employed for quantitative data. All the tests were two-tailed, and a P value of less than 0.05 was considered significant. Results: Among the patients with AML, 65% had a high Cx32 expression level, whereas 63.3% had a low Cx43 expression level. There was a statistically significant difference in the fold change values of Cx32 and Cx43 expression between the patient group and the control group (P=0.009 vs P=0.013, respectively). There was a remarkable association between both Cxs and CD34 and HLA-DR cells. Conclusion: Cx expression in samples may add to the diagnostic workup of AML. Although we found a negative correlation between Cx43 expression and the peripheral blood blast percentage, the response after the first induction of chemotherapy showed no significant relationship with Cx43 and Cx32.

Non-specific colitis among patients with colitis: frequency and relation to inflammatory bowel disease, a prospective study / Colite inespecífica entre pacientes com colite: estudo prospectivo sobre sua frequência e relação com doença inflamatória intestinal

Abstract Background and study aim: The term non-specific colitis refers to an inflammatory condition of the colon that microscopically lacks the characteristic features of any specific form of colitis and is commonly seen in pathology reports of colonoscopy biopsies. In fact, it has been questioned whether it is a separate pathological entity or it is merely an intermediate stage in the course of inflammatory bowel disease. This study was conducted to estimate the prevalence of non-specific colitis among patients with colitis and characterize its natural history over a 6 months year period. Patients and methods: Eighty adult patients presented for colonoscopy were enrolled. In the final analysis they were divided into Group A; the non-specific colitis Group and Group B; the inflammatory bowel disease Group. All patients were subjected to: full history taking, full clinical examination, laboratory investigations: which included stool analysis, CRP, ESR, complete colonoscopy and entire random colon biopsies for histopathological examination. Results: Group A included 67 patients (83.75%) while Group B included 13 (16.25%) patients. Patients with IBD had clinical and laboratory features of inflammation significantly higher than patients with non-specific colitis. Six patients (8.95%) of non-specific colitis group developed histologic features of florid inflammatory bowel disease after 6 months. There were no independent predictors of this conversion. Conclusion: Among our 80 patients with colonoscopy and biopsy 67 (83.75%) were diagnosed as non-specific colitis and out of them 6 patients (8.95%) were reexamined after 6 months and proved to have inflammtory bowel disese this change was not linked to predictive factors.

Resumo Introdução e objetivos: O termo colite inespecífica (CI) refere-se a uma condição inflamatória do cólon que microscopicamente não apresenta características de qualquer forma específica de colite; é comumente observada em relatórios patológicos de biópsias de colonoscopia. De fato, tem-se questionado se esta seria uma entidade patológica separada ou apenas um estágio intermediário no curso da DII. Este estudo foi realizado para estimar a prevalência de CI entre pacientes com colite e caracterizar seu curso durante um período de seis meses. Pacientes e métodos: O estudo incluiu 80 pacientes adultos que se apresentaram para colonoscopia. Na análise, os pacientes foram divididos em dois grupos: grupo A (CI) e grupo B (DII) Todos os pacientes foram submetidos a anamnese completa, exame clínico completo e investigações laboratoriais que incluíram análise de fezes, PCR, VHS, colonoscopia completa e biópsias aleatórias de cólon para exame histopatológico. Resultados: Do total de pacientes, 67 foram alocados no grupo A (83,75%) e 13 (16,25%) no grupo B. Os pacientes com DII apresentavam sinais clínicos e laboratoriais de inflamação significativamente maiores do que o observado em pacientes com CI. Seis pacientes (8,95%) do grupo CI desenvolveram características histológicas de DII florida após seis meses. Não foram identificados preditores independentes para essa conversão. Conclusão: Entre os 80 pacientes submetidos a colonoscopia e biópsia, o diagnóstico de CI foi feito em 67 (83,75%); destes, seis pacientes (8,95%) foram reexaminados após seis meses e apresentaram DII, sendo que essa conversão não foi associada a fatores preditivos.

DOG1 immunohistochemical staining of testicular biopsies is a reliable tool for objective assessment of infertility.

Testicular biopsy may be a component of the work-up of male infertility. However, no reliable diagnostic tools are available for objective quantitative assessment of spermatogenic cells. It is well known that MAGE-A4 is selectively expressed in spermatogonia and our group has previously demonstrated that DOG1 differentially stains germ cells. Therefore, we performed DOG1 and a double stain cocktail (DOG1 and 57b murine monoclonal anti-MAGE-A4) immunohistochemical stains on 40 testicular infertility biopsies (10 each with active spermatogenesis, Sertoli cell-only, hypospermatogenesis, and maturation arrest), 25 benign seminiferous tubules from radical orchiectomies, and 5 spermatocytic tumors (ST). In biopsies/resections with active spermatogenesis, DOG1 stained spermatocytes and spermatids and was absent in spermatogonia, while MAGE-A4 stained spermatogonia and primary spermatocytes (weak). In hypospermatogenesis, DOG1 highlighted decreased spermatocytes/spermatids and MAGE-A4 highlighted decreased spermatogonia. DOG1 staining confirmed decreased to absent spermatocytes in maturation arrest and MAGE-A4 staining established the presence of preserved spermatogonia in all cases. All STs were negative for DOG1 and positive for MAGE-A4, while all Sertoli cell-only cases were negative for DOG1 and the double stain cocktail. In conclusion, we confirmed that DOG1 is expressed in spermatocytes and spermatids and MAGE-A4 highlights primarily spermatogonia. Usage of these stains facilitates confirmation of maturation arrest, assessment of the percentage of testis involvement in hypospermatogenesis and identification of mixed patterns. Finally, this study supports that the differentiation of STs is more closely related to spermatogonia than the more mature spermatocytes.

Erlotinib resistance in lung cancer: current progress and future perspectives.

Lung cancer is the most common cancer in the world. Despite modern advancements in surgeries, chemotherapies, and radiotherapies over the past few years, lung cancer still remains a very difficult disease to treat. This has left the death rate from lung cancer victims largely unchanged throughout the past few decades. A key cause for the high mortality rate is the drug resistance that builds up for patients being currently treated with the chemotherapeutic agents. Although certain chemotherapeutic agents may initially effectively treat lung cancer patients, there is a high probability that there will be a reoccurrence of the cancer after the patient develops resistance to the drug. Erlotinib, the epidermal growth factor receptor (EGFR)-targeting tyrosine kinase inhibitor, has been approved for localized as well as metastatic non-small cell lung cancer where it seems to be more effective in patients with EGFR mutations. Resistance to erlotinib is a common observation in clinics and this review details our current knowledge on the subject. We discuss the causes of such resistance as well as innovative research to overcome it. Evidently, new chemotherapy strategies are desperately needed in order to better treat lung cancer patients. Current research is investigating alternative treatment plans to enhance the chemotherapy that is already offered. Better insight into the molecular mechanisms behind combination therapy pathways and even single molecular pathways may help improve the efficacy of the current treatment options.