Acute kidney injury and other renal disorders are thought to be primarily caused by renal ischemia-reperfusion (RIR). Cyclic adenosine monophosphate (cAMP) has plenty of physiological pleiotropic effects and preserves tissue integrity and functions. This research aimed to examine the potential protective effects of the β3-adrenergic receptors agonist mirabegron in a rat model of RIR and its underlying mechanisms. Male rats enrolled in this work were given an oral dose of 30 mg/kg mirabegron for two days before surgical induction of RIR. Renal levels of kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), Interleukin-10 (IL-10), cAMP, cAMP-responsive element binding protein (pCREB), and glycogen synthase kinase-3 beta (GSK-3β) were assessed along with blood urea nitrogen and serum creatinine. Additionally, caspase-3 and nuclear factor-kappa B (NF-κB) p65 were explored by immunohistochemical analysis. Renal specimens were inspected for histopathological changes. RIR led to renal tissue damage with elevated blood urea nitrogen and serum creatinine levels. The renal KIM-1, MCP-1, TNF-α, and GSK-3β were significantly increased, while IL-10, cAMP, and pCREB levels were reduced. Moreover, upregulation of caspase-3 and NF-κB p65 protein expression was seen in RIR rats. Mirabegron significantly reduced kidney dysfunction, histological abnormalities, inflammation, and apoptosis in the rat renal tissues. Mechanistically, mirabegron mediated these effects via modulation of cAMP/pCREB and GSK-3β/NF-κB p65 signaling pathways. Mirabegron administration could protect renal tissue and maintain renal function against RIR.
Toxoplasma gondii infection remains a significant global health concern, promoting the urgent need
for effective therapeutic strategies. This study aimed to evaluate the therapeutic potential of chitosan
nanoparticles (CSNPs) and curcumin-loaded chitosan nanoparticles (Cur-CSNPs) against the chronic
Toxoplasma gondii (ME49 strain) in an experimental mouse model. This achieved by investigating
their ability to reduce parasitic load, oxidative stress, histopathological lesion, and to enhance the
host immune response. Sixty female BALB/c mice were divided into five groups: infected untreated
group, Spiramycin®-treated group, CSNPs-treated group, Cur-CSNPs-treated group, and negative
control group. The Cur-CSNPs-treated group exhibited the lowest brain cyst counts, along with
significant reductions in cyst size. Hematological indices revealed no significant reduction in total
white blood cell (WBC) counts or in the percentage of neutrophils, monocytes, and eosinophils in
both the CSNPs and Cur-CSNPs treated groups, compared to the infected untreated group and
Spiramycin-treated group. However, both nanoparticle-treated groups exhibited a significant decrease
in the percentage of lymphocytes compared to the infected untreated group. Significant differences
in total antioxidant capacity (TAC) and malondialdehyde (MDA) levels were observed, with the
Cur-CSNPs treated group displaying values comparable to the negative control. Histopathological
examination revealed substantial improvements in the brain, liver, and spleen tissues of Cur-CSNPstreated
animals, characterized by preserved tissue architecture and reduced inflammatory lesions.
Immunohistochemical analysis further revealed reduced expression of IL-6 and TNF-α, indicating a
mitigated inflammatory response. These findings highlight the promising therapeutic role of Cur-
CSNPs in controlling chronic T. gondii infection and suggest their potential as a novel strategy for
developing effective antiparasitic treatments.
Keywords Toxoplasma, Curcumin, Chitosan nanoparticles, Oxidative stress, TNF-α, Histopathological
lesions
is frequent, loose, or watery bowel movements (BMs) that differ from a child's normal
pattern, as is a very common problem, leading cause of child mortality and morbidity worldwide.
In children acute watery diarrhea (several hours or days), acute bloody diarrhea (dysentery), and
persistent diarrhea, which lasts 14 days or longer. Gastroenteritis most common symptoms regardless
of cause, are vomiting, diarrhea, and sometimes abdominal cramps, fever, and poor appetite.
The risky complication of gastroenteritis is dehydration. The dehydrated children become listless,
irritable, or sluggish (lethargic), but dehydrated infants develop serious side effects with hospitalized
medical care. The causative agents of diarrhea in children are viruses, particularly rotavirus
(preventable with a vaccine) and norovirus, as well as adenovirus and arbovirus, bacteria
like E. coli, salmonella and cholera. Protozoal parasites causing diarrhea as Cryptosporidium, Entamoeba,
Giardia, Balantidium coli and Cystoisospora belli as well as helminths as Strongyloides,
Schistosoma and Trichuris may cause chronic diarrhea especially in immunocompromised individuals.
Apart from microorganism agents, diet, antibiotics and others can cause children diarrhea.
Key words: Children, Diarrhea, Pathogenesis, Bacteria, Parasites, Viruses, Others
Background: Bladder cancer preservation treatment achieved 5/10-year overall survival rates comparable to those of radical cystectomy. Bladder-preserving trials have recommended coverage of pelvic lymph nodes (LN) in radiation portals (micrometastases in pelvic LN 25 to 44%). Gemcitabine-based radiotherapy did not include the pelvic LN in the radiation portals to minimize bowel toxicity. However, the pelvic LN irradiation debate has been highlighted. The present study aimed to evaluate the role of pelvic LN irradiation in negative node, bladder cancer.
Method: A prospective study was conducted from October 2017 to February 2020 at the South Egypt Cancer Institute. Bladder cancer Patients with cT1-3, N0, and M0 underwent maximum TURBT and were then randomized into two arms: Group A: Bladder-only irradiation (52.5 GY/20 frs); Group B: Pelvic nodal irradiation with weekly gemcitabine 100mg/m2
Statistical analysis: SPSS Statistics (version 26.0, IBM), descriptive (means and SD), chi-square test for qualitative variables, independent student t-test, and survival analysis (Kaplan-Meier).
Results: Patients aged 37 to 76 years old and 32 to 82 years old in groups A and B, respectively. Cases were Stage III in groups A, II, and III in B. Both groups showed similar local control rates (90% and 92%, respectively). Favorable toxicity profile group A schedule emphasizes high local control with low-grade intestinal toxicity (no G3 enteritis). Unexpectedly, Group A showed significantly higher progression free survival (PFS over Group B (P < 0.034).
Conclusion: Bladder-only chemoradiation has non-inferior local control of node-negative bladder cancer with significantly higher PFS. The pelvic nodal radiation field has an unfavorable toxicity profile (higher G2 enteritis).
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Cardiovascular diseases have become a leading global health burden, with rising mortality worldwide. WNT and JAK/STAT have been highlighted as emerging biomarkers in cardiovascular disease pathogenesis. This study assessed the Wnt/JAK-STAT signaling pathway in relation to SFRP5 and genetic polymorphisms in cardiac patients. This prospective case–control study included 100 patients with various cardiac diseases (IHD, valvular heart disease, HF, cardiomyopathy, and arrhythmia) and 50 matched healthy controls. Clinical and echocardiographic assessments were performed. Plasma SFRP5, Wnt5a, and JAK levels were measured using ELISA; STAT5A expression by flow cytometry; and SFRP5 (rs780369540) gene polymorphism by TaqMan real-time PCR were also performed in all participants. Cardiac patients showed significantly higher median BMI (33 vs. 28.5 kg/m2, p = 0.001) and markedly increased median value of each Wnt5a (16.85 vs. 5.6 pg/mL, p < 0.001), median JAK (9.45 vs. 2.4 pg/mL, p < 0.001), and STAT5A expression (87.55% vs. 33%, p < 0.001), with lower SFRP5 levels (4 vs. 6.7 ng/L, p < 0.001) compared to control. The SFRP5 (rs780369540) T allele was more frequent in patients (51.5% vs. 32%, p = 0.001), and dominant TT + TC genotypes were higher (66% vs. 42%, p = 0.005) compared to the control group. TT carriers showed higher median Wnt5a, lower median SFRP5, and reduced ejection fraction compared to other genotypes (TC, CC) carriers. Multivariate analysis identified elevated Wnt5a, JAK, and decreased SFRP5 as independent predictors of cardiovascular disease (p < 0.05). Cardiac patients …