Hepatitis C Virus (HCV) Vertical Transmission in 12-Month-Old Infants Born to HCV-Infected Women and Assessment of Maternal Risk Factors

Background. Hepatitis C virus (HCV) is an underappreciated cause of pediatric liver disease, most frequently acquired by vertical transmission (VT). Current guidelines that include the option of screening infants for HCV RNA at 1–2 months are based on data prior to current real-time polymerase chain reaction (PCR)-based testing. Previous studies have demonstrated VT rates of 4%–15% and an association with high maternal viral load. We evaluated HCV RNA in infants with HCV VT and assessed maternal risk factors in a prospective cohort in Cairo, Egypt

Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the colorectal area that demonstrates a dramatically increasing incidence worldwide. This study provides novel insights into the capacity of the exogenous β-hydroxybutyrate and ketogenic diet (KD) consumption to alleviate dextran sodium sulfate (DSS)-induced UC in rats. Remarkably, both interventions attenuated disease activity and colon weight-to-length ratio, and improved macro and microstructures of the damaged colon. Importantly, both β-hydroxybutyrate and KD curbed the DSS-induced aberrant NLRP3 inflammasome activation as observed in mRNA and protein expression analysis. Additionally, inhibition of the NLRP3/NGSDMD-mediated pyroptosis was detected in response to both regimens. In parallel, these modalities attenuated caspase-1 and its associated consequences of IL-1β and IL-18 overproduction. They also mitigated apoptosis as indicated by the inactivation of caspase-3. The anti-inflammatory effects of BHB and KD were confirmed by the reported decline in the levels of inflammatory markers including MPO, NFκB, IL-6, and TNF-α. Moreover, these interventions exhibited antioxidative properties by reducing ROS production and improving antioxidative enzymes. Their effectiveness in mitigating UC was also evident in the renovation of normal intestinal epithelial barrier function, as shown by correcting the discrepancies in the levels of tight junction proteins ZO-1, OCLN, and CLDN5. Furthermore, their effects on the intestinal microbiota homeostasis were investigated. In terms of autophagy, exogenous β-hydroxybutyrate upregulated BECN-1 and downregulated p62, which may account for its superiority over KD in attenuating colonic damage. In conclusion, this study provides experimental evidence supporting the potential therapeutic use of β-hydroxybutyrate or β-hydroxybutyrate-boosting regimens in UC

Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Therapeutic effect of adipose-derived mesenchymal stem cells (AD-MSCs) compared to pirfenidone on corticosteroid resistance in a mouse model of acute exacerbation of idiopathic pulmonary fibrosis

Introduction. Acute exacerbation-idiopathic pulmonary fibrosis (AE-IPF) is a life-threatening condition. In the treatment of AE-IPF, corticosteroid medication is commonly utilized. However, there is insufficient evidence to justify its usage. Pirfenidone (PFD) has recently been discovered to be effective in the treatment of AE-IPF patients. However, regenerative therapy, such as stem cell therapy or tissue engineering, is necessary due to ineffective and limited therapies. Combining MSC transplantation with pharmacological therapy may also give additional benefits; nevertheless, its use must be proven experimentally. As a result, the goal of this study was to assess the therapeutic effects of adipose-derived mesenchymal stem cells (AD-MSCs) on corticosteroid resistance in an animal model of AE-IPF caused by bleomycin compared to PFD. Materials and methods. Seventy C57BL/6J male mice were randomly divided into seven groups, control, BLM, methylprednisolone (MP), PFD, AD-MSCs, PFD +MP, and AD-MSCs +MP. Results. In terms of survival, collagen deposition, the acute lung injury score (ALI), and the Ashcroft score, AD-MSCs exceeded PFD. AD-MSCs + MP provided protection and preserved the lung's architecture in BLM-induced AE. In addition, AD-MSCs successfully decreased chemokine (CC motif) ligand-2 (CCL2) positive cells and lower pro-fibrotic and proinflammatory cytokines. Conclusions. AD-MSCs enhanced histological structure, Ashcroft and ALI scores, lung collagen deposition, survival, and cytokines in an animal model of AE-IPF. As a result, we believe that AD-MSCs may be more therapeutically helpful for AE-IPF than presently available therapies, either alone or in conjunction with MP

Cytokeratin 18 as a non invasive marker in diagnosis of NASH and its usefulness in correlation with disease severity in Egyptian patients

Background: A simple noninvasive test that accurately distinguishes NASH from NAFL as well as determines the disease severity is urgently needed. Recently, it was found that determination of cytokeratin-18 (CK-18) fragments in the blood, predicts and correlates with histological NASH in which there is development of lobular inflammation, cell ballooning and fibrosis, supporting its usefulness in clinical practice. Aims: To evaluate the role of CK-18 as a non invasive marker in diagnosis of NASH and its usefulness in correlation with disease severity in Egyptian patients. Patients and methods: 90 subjects were divided into 3 groups: group I: including 30 patients with NASH, group II: including 30 patients with NAFL, and group III: including 30 healthy subjects as control. Diagnosis of NASH and its discrimination from NAFL was done by liver biopsy. CK-18 level in plasma was measured for all subjects using ELISA. Results: CK-18 was significantly elevated in patients of group I in comparison to group II and III patients, with mean ± SD: 460 ± 279, 167 ± 56 and 149 ± 57, respectively, and P value: 0.001. The (ROC) curve diagnostic performance of CK18 in diagnosis of NASH shows: cutoff value of >240 U/L, with sensitivity 76.7%, specificity 95.0%. Ck-18 was found to correlate with disease severity assessed by NAS scoring system with P value: 0.001. Conclusion: Measurement of CK18 in NASH is a useful screening, diagnostic and staging biomarker

Obesity Risk Prediction among Women of Upper Egypt: The impact of FTO rs17817449 gene polymorphism, serum ghrelin and high sensitivity C- reactive protein

Obesity is one of the main threats to the human health. It is a major risk factor for hyperinsulinemia, hypertension, hyperlipidemia, type II diabetes mellitus, and atherosclerotic cardiovascular disease. FTO gene variants have been associated with obesity and diabetes mellitus in different populations, but its role in the susceptibility of these diseases remains unknown. The present study is undertaken to assess the contribution of the FTO rs17817449 gene variants towards obesity and diabetes development and to evaluate the role of ghrelin and hs- CRP on the outcome of obesity in the Upper Egyptian women. A total of 229 subjects, 115 obese (65 non diabetics, 50 diabetics) and 114 non obese non diabetic controls were included in this case control study. Genotyping of FTO gene rs17817449 (T>G) polymorphism was performed by mutagenically separated PCR (MS-PCR) method. Estimation of serum gherlin, hs-CRP levels, related anthropometric and metabolic parameters were performed. The results revealed higher frequency of FTO rs17817449 G allele among obese subjects (46.5%) and obese diabetics (45%) compared to the controls (33.3%) which comprise about 1.75 times increase in the risk for obesity (p<0.01). The distribution of the GG and TG genotypes of FTO were 25.2%, and 42.6% among obese non diabetic, 24% and 42% among obese diabetic and 14.9% and 36.8% among controls respectively. FTO-GG genotype variant was significantly associated with weight, BMI and waist and hip circumference (p<0.05 for each). FTO GG carriers had 2.54 times the possibility to have obesity more than TT carriers. Ghrelin levels were significantly decreased and hs-CRP levels were significantly increased in obese subjects compared to the controls (P<0.001 for each). There was a significant negative correlation between serum ghrelin and hs-CRP (p<0.05). No significant association was detected between FTO genotypes and each of ghrelin, hs-CRP, lipid profile, fasting glucose or insulin levels. In conclusion, the G allele of FTO rs17817449 genotyping is associated with increased obesity risk but there is a lack of association with diabetes. It is also associated with some obesity indices as BMI, hip and waist circumference in the Upper Egyptian women. Both Ghrelin and hs- CRP could play a role in developing obesity. To the best of our knowledge, this is the first study of FTO SNP in Upper Egyptian women. Switching off this FTO faulty gene variant by the recent therapies (as certain foods or gene therapy) will prevent the percentage of women who is affected by this risk allele to get obese via burning rather than storing energy.Key words: FTO gene polymorphism, ghrelin, hs-CRP, Obesit

Ganetespib (STA-9090) augments sorafenib efficacy via necroptosis induction in hepatocellular carcinoma: Implications from preclinical data for a novel therapeutic approach

Sorafenib, a multikinase inhibitor, is a first-line treatment for advanced hepatocellular carcinoma, but its long-term effectiveness is limited by the emergence of resistance mechanisms. One such mechanism is the reduction of microvessel density and intratumoral hypoxia caused by prolonged sorafenib treatment. Our research has demonstrated that HSP90 plays a critical role in conferring resistance to sorafenib in HepG2 cells under hypoxic conditions and N-Nitrosodiethylamine-exposed mice as well. This occurs through the inhibition of necroptosis on the one hand and the stabilization of HIF-1α on the other hand. To augment the effects of sorafenib, we investigated the use of ganetespib, an HSP90 inhibitor. We found that ganetespib activated necroptosis and destabilized HIF-1α under hypoxia, thus enhancing the effectiveness of sorafenib. Additionally, we discovered that LAMP2 aids in the degradation of MLKL, which is the mediator of necroptosis, through the chaperone-mediated autophagy pathway. Interestingly, we observed a significant negative correlation between LAMP2 and MLKL. These effects resulted in a reduction in the number of surface nodules and liver index, indicating a regression in tumor production rates in mice with HCC. Furthermore, AFP levels decreased. Combining ganetespib with sorafenib showed a synergistic cytotoxic effect and resulted in the accumulation of p62 and inhibition of macroautophagy. These findings suggest that the combined therapy of ganetespib and sorafenib may offer a promising approach for the treatment of hepatocellular carcinoma by activating necroptosis, inhibiting macroautophagy, and exhibiting a potential antiangiogenic effect. Overall, continued research is critical to establish the full therapeutic potential of this combination therapy

Accelerating Hepatitis C virus elimination in Egypt by 2030: A national survey of communication for behavioral development as a modelling study.

Aim of the workThis study aimed at assessing the dominance of risk practices associated with HCV endemicity in Egypt and detecting the behavioral development level concerning different aspects of HCV risk behaviors with respect to age and gender. The survey highlights the most cost-effective strategies that could accelerate HCV elimination in Egypt.Subjects and methodsA national household survey targeted 3780 individuals (age range: 10-85 years). The sample was a systematic probability proportionate to size from 6 governorates representing the six major subdivisions of Egypt. The indicators used for assessing the behavioral development level towards HCV included six domains: awareness (7 indicators), perceived risk (5 indicators), motivation with the intention to change (4 and 5 indicators for males and females respectively), trial, rejection or adoption (6 and 5 indicators for males and females respectively).ResultsThe study revealed that along the continuum of behavior development, the percentage of the participants who acquired half of the scores was as follows: 73.1% aware, 69.8% developed perceived risk, 80.6% motivated with only 28.9% adopting the recommended behaviors, 32% rejected them, 2.3% were in the trial stage versus 35.8% who did not try any. Adolescents had significantly lower levels of development for almost all domains when compared to adults. Statistical higher significance was detected in favor of adults, employees, married, Lower Egypt governorates, and university-educated participants (pConclusionEgypt would be closer to HCV elimination when cost-effective strategies are directed not towards creating awareness, perceived risk or motivation to change- (at an acceptable level)- but towards motivating adopting risk-reduction behaviors for HCV, tackling misconceptions and reinforcement of social support