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Mixed lineage kinase domain-like pseudokinase (MLKL), one of the main downstream components of the necroptosis or programmed necrosis has recently been demonstrated in advanced atherosclerotic lesions. However, its precise role in the atherosclerosis pathogenesis still requires more elucidation. Our study was set to delineate both the changes in peripheral MLKL gene expression and its influence on disease severity in atherosclerotic patients with and without type 2 diabetes mellitus. The study involved 50 patients (20 non-diabetics and 30 diabetics) undergoing coronary artery bypass graft and 20 apparently healthy controls. Taqman RT-PCR was used to quantify MLKL mRNA expression levels, while ELISA was employed to estimate serum insulin and high sensitivity C-reactive protein (hsCRP) levels. Compared with the control group, MLKL gene was up regulated significantly in cardiovascular diseases (CVD; p ≤ 0.001). Higher MLKL expression was demonstrated in diabetic CVD group than non-diabetic group (p < 0.05). Correlation studies reported positive associations between MLKL and markers of dyslipidemia, inflammation, and insulin resistance. Multiple regression analysis revealed that FBG levels, hsCRP levels, and total white blood cells count were significant predictors for MLKL levels. Receiver operating characteristic curve showed a significant diagnostic value of MLKL for CVD. Moreover, regression analysis demonstrated that MLKL and hsCRP were independent predicting factors for the severity of CVD. MLKL is linked to hallmarks of atherosclerosis and could explain increased cardiovascular risk in diabetic patients. Thus, it can be a potential drug target for treatment of atherosclerotic patients.

We aimed to determine the incidence of trichomoniasis and its risk factors in Egyptian pregnant women attending the Minia Maternity and Pediatric University Hospital, Minia, Egypt and evaluate its association with preterm birth. The study was carried out from Aug 2014 to Jun 2015 through 2 phases, the first phase was case-control study, and the second phase was follow-up with intervention. Overall, 300 pregnant women with gestational age of 20-36 weeks with no medical risk factors of preterm labour birth were enrolled. Vaginal swabs were examined by the wet mount microscopy and culture while urine samples were examined by urine analysis. Demographic information was collected. Pregnant women were divided into two groups, study group (with trichomoniasis) and control group (without trichomoniasis). Positive cases were subjected to metronidazole treatment. Thirty-five cases were positive for infection. Maximum cases were detected by culture (11.7%) followed by wet mount microscopy (9.7%) whereas least number of cases (7.3%) was detected by urine examination. Nineteen (54.28%) cases had preterm delivery. Post-delivery adverse outcomes were observed in 29 cases (82.8%). The high rate of infection was observed in age group of 20-30 years ( <0.05). In addition, there was a significant infection in pregnant women living in rural area, of low socioeconomic and primary educational levels ( <0.05). Pregnant women lived in rural area with a low socioeconomic and primary educational levels should be screened for trichomoniasis to reduce the incidence of preterm delivery and low birth weight.

Aedes aegypti and Ae. albopictus are the primary vectors that transmit several arboviral diseases, including dengue, chikungunya, and Zika. The world is presently experiencing a series of outbreaks of these diseases, so, we still require to better understand the current distributions and possible future shifts of their vectors for successful surveillance and control programs. Few studies assessed the influences of climate change on the spatial distributional patterns and abundance of these important vectors, particularly using the most recent climatic scenarios. Here, we updated the current potential distributions of both vectors and assessed their distributional changes under future climate conditions. We used ecological niche modeling approach to estimate the potential distributions of Ae. aegypti and Ae. albopictus under present-day and future climate conditions. This approach fits ecological niche model from occurrence records of each species and environmental variables. For each species, future projections were based on climatic data from 9 general circulation models (GCMs) for each representative concentration pathway (RCP) in each time period, with a total of 72 combinations in four RCPs in 2050 and 2070. All ENMs were tested using the partial receiver operating characteristic (pROC) and a set of 2,048 and 2,003 additional independent records for Ae. aegypti and Ae. albopictus, respectively. Finally, we used background similarity test to assess the similarity between the ENMs of Ae. aegypti and Ae. albopictus. The predicted potential distribution of Ae. aegypti and Ae. albopictus coincided with the current and historical known distributions of both species. Aedes aegypti showed a markedly broader distributional potential across tropical and subtropical regions than Ae. albopictus. Interestingly, Ae. albopictus was markedly broader in distributional potential across temperate Europe and the United States. All ecological niche models (ENMs) were statistically robust (P < 0.001). ENMs successfully anticipated 98% (1,999/2,048) and 99% (1,985/2,003) of additional independent records for both Ae. aegypti and Ae. albopictus, respectively (P < 0.001). ENMs based on future conditions showed similarity between the overall distributional patterns of future-day and present-day conditions; however, there was a northern range expansion in the continental USA to include parts of Southern Canada in case of Ae. albopictus in both 2050 and 2070. Future models also anticipated further expansion of Ae. albopictus to the East to include most of Europe in both time periods. Aedes aegypti was anticipated to expand to the South in East Australia in 2050 and 2070. The predictions showed differences in distributional potential of both species between diverse RCPs in 2050 and 2070. Finally, the background similarity test comparing the ENMs of Ae. aegypti and Ae. albopictus was unable to reject the null hypothesis of niche similarity between both species (P > 0.05). These updated maps provided details to better guide surveillance and control programs of Ae. aegypti and Ae. albopictus. They have also significant public health importance as a baseline for predicting the emergence of arboviral diseases transmitted by both vectors in new areas across the world.

Through our present study, three novel Gemini-fluorinated cationic surfactants bearing different spacers (FSG6-2, FSG6-4, and FSG6-6) were synthesized, and their structures were explained via different spectroscopic instruments such as 1H, 13C, and 19F NMR spectra. The surface activity of the as-prepared surfactants was examined. The inhibiting influence of FSG6 molecules on the X60 steel corrosion in the pickling solution (HCl) was examined by diverse methods comprising electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PDP), and X-ray photoelectron spectroscopy (XPS) experimentations, and computational calculations. The inhibition effectiveness of FSG6 surfactants followed the order of 93.37% (FSG6-2) < 96.74% (FSG6-4) < 98.37% (FSG6-6) at 2.0 × 10−4 M. The FSG6 surfactants function as mixed-type inhibitors, according to PDP investigations. The H2O molecules that adsorbed on the steel interface were substituted with surfactant molecules, and the surfactant’s inhibitory activity is likely caused by the improvement in an adsorptive layer on the steel substrate, as specified by the EIS results. The Langmuir isotherm describes the absorption of FSG6 molecules on the metal surface. The XPS investigations validate the steel interface’s extremely protective nature. The mechanism of interaction between FSG6 molecules with an X60-steel employing the DFT calculations and MC simulations methods was also examined and discussed.

Objective: To propose a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery and increased bioavailability in treating Huntington’s disease (HD). Methods: We conducted a literature review of the pathophysiology of HD and the limitations of currently available medications. We also reviewed the potential therapeutic benefits of engeletin, a flavanol glycoside, in treating HD through the Keap1/nrf2 pathway. We then proposed a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery across the blood-brain barrier (BBB) and increased bioavailability. Results: HD is an autosomal dominant neurological illness caused by a repetition of the cytosine-adenine-guanine trinucleotide, producing a mutant protein called Huntingtin, which degenerates the brain’s motor and cognitive functions. Excitotoxicity, mitochondrial dysfunction, oxidative stress, elevated concentration of ROS and RNS, neuroinflammation, and protein aggregation significantly impact HD development. Current therapeutic medications can postpone HD symptoms but have long-term adverse effects when used regularly. Herbal medications such as engeletin have drawn attention due to their minimal side effects. Engeletin has been shown to reduce mitochondrial dysfunction and suppress inflammation through the Keap1/NRF2 pathway. However, its limited solubility and permeability hinder it from reaching the target site. A theoretical formulation of engeletin-nanostructured lipid nanocarriers may allow for free transit over the BBB due to offering a similar composition to the natural lipids present in the body a lipid solubility and increase bioavailability, potentially leading to a cure or prevention of HD. Conclusion: The theoretical formulation of engeletin-nanostructured lipid nanocarriers has the potential to improve delivery and increase the bioavailability of engeletin in the treatment of HD, which may lead to a cure or prevention of this fatal illness.

Probiotics serve as promising candidates in type 2 diabetes mellitus (T2DM) therapy. Not only they presumably reduce the T2DM prevalence, but also keep down its complications. In the present study, we explored the beneficial impact of ZBiotics, an engineered probiotic, on T2DM Wistar rats. In silico analysis was performed to construct a genetic-epigenetic network linked to STING-NOD pathway and autophagy signaling. Then, 30 Wistar rats were divided into 5 groups (each n = 6); normal group, diabetic model, B. subtilis , and ZBiotics treated rats at high and low doses. Experimental procedures were carried out including biochemical and histopathologic analyses. Samples were extracted from rats’ blood, liver, kidney and adipose tissues. At the molecular aspect, the molecular players, chosen by the in silico analysis, were assessed using 2 –ΔΔCt to estimate their relative quantification. With immunohistochemistry, TNF-alpha and LC3B were assessed as reflectors for inflammation and autophagy respectively. ZBiotics was reported to ameliorate the T2DM-induced histological damage. Besides, it downregulated TNF-alpha and upregulated LC3B expression levels. At the biochemical aspect, ZBiotics corrected LDL-c and improved serum creatinine and CK-MB levels. Inflammation relevant genes have been downregulated regarding CHUK, NFKB1 and miR-611. Therefore, ZBiotics is speculated to operate by modulating the genetic-epigenetic network linked to inflammatory cGAS-STING and autophagy signaling. ZBiotics is recommended for clinical trials as a separate candidate or as an adjuvant to the conventional T2DM therapy.

Novel three-dimensional biodegradable porous nanocomposite bone scaffolds were fabricated using acacia gum and gelatin as the base polymer matrix and magnesium doped nano hydroxyapatite as cementing materials using gamma irradiation facility for crosslinking and sterilization processes. Mg-doped HAp nanoparticles were synthesized using wet chemical method. XRD studies verified the nano-scale size of the prepared HAp. In addition to Ca and P in the prepared n-HAp, the EDX analysis revealed the presence of Mg in the doped HAp samples. FTIR studies confirmed the existence of the characteristic functional groups of the scaffold constituents. The swelling behavior was found to be dependent on the quantity of embedded HAp nanoparticles. Nanocomposite scaffold porosity ranged from 26 to 39%, which increased with the inclusion of Mg ions. The developed scaffolds showed appropriate mechanical properties that enhanced by the existence of HAp nanoparticles. The incorporation of the Mg-doped HAp nanoparticles encourages the development of bone-like apatite layer. In vitro cytotoxicity assessment and blood compatibility demonstrated their biocompatibility. The developed scaffolds show promising antibacterial activity against Staphylococcus aureus and Escherichia coli. In vitro drug release study showed that the loaded Ketoprofen scaffolds were able to deliver the loaded drug sustainably.

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has a disastrous effect on mankind due to the contagious and rapid nature of its spread. Although vaccines for SARS-CoV-2 have been successfully developed, the proven, effective, and specific therapeutic molecules are yet to be identified for the treatment. The repurposing of existing drugs and recognition of new medicines are continuously in progress. Efforts are being made to single out plant-based novel therapeutic compounds. As a result, some of these biomolecules are in their testing phase. During these efforts, the whole-genome sequencing of SARS-CoV-2 has given the direction to explore the omics systems and approaches to overcome this unprecedented health challenge globally. Genome, proteome, and metagenome sequence analyses have helped identify virus nature, thereby assisting in understanding the molecular mechanism, structural understanding, and disease propagation. The multi-omics approaches offer various tools and strategies for identifying potential therapeutic biomolecules for COVID-19 and exploring the plants producing biomolecules that can be used as biopharmaceutical products. This review explores the available multi-omics approaches and their scope to investigate the therapeutic promises of plant-based biomolecules in treating SARS-CoV-2 infection.

Background: Amiodarone is widely used for heart arrhytmia. Previous studies have suggested the possibility of optic neuropathy with the chronic use of this drug. Objectives: To identify structural or functional changes in the retina and optic nerve in patients on chronic amiodarone therapy without visual complaints. Methods: This observational study included 15 eyes of 15 patients with cardiac arrythmia on chronic amiodarone treatment and 15 healthy matched subjects as a control group. All subjects underwent electrophysiological tests [pattern visual evoked potential (PVEP), pattern electroretinogram (PERG), multifocal electroretinogram (mfERG), and optical coherence tomography (OCT) and angiography (OCTA)]. Results: There were no statistically significant differences between the two groups regarding the PVEP, PERG, and the mfERG parameters. Macular and optic nerve head OCT and OCTA have not shown statistically significant differences except for the morphological parameters of the optic disc (p = 0.008 for the horizontal and p = 0.013 for vertical cup/disc ratio and p = 0.045 for rim area). Conclusion: Patients on chronic amiodarone therapy have not shown evident structural or functional changes in the retinal or optic nerve as demonstrated by electrophysiological tests, OCT, and OCTA results compared to controls.