Investigating the Association between the Autophagy Markers LC3B, SQSTM1/p62, and DRAM and Autophagy-Related Genes in Glioma.

High-grade gliomas are extremely fatal tumors, marked by severe hypoxia and therapeutic resistance. Autophagy is a cellular degradative process that can be activated by hypoxia, ultimately resulting in tumor advancement and chemo-resistance. Our study aimed to examine the link between autophagy markers' expression in low-grade gliomas (LGGs) and high-grade gliomas (HGGs). In 39 glioma cases, we assessed the protein expression of autophagy markers LC3B, SQSTM1/p62, and DRAM by immunohistochemistry (IHC) and the mRNA expression of the autophagy genes PTEN, PI3K, AKT, mTOR, ULK1, ULK2, UVRAG, Beclin 1, and VPS34 using RT-qPCR. LC3B, SQSTM1/p62, and DRAM expression were positive in 64.1%, 51.3%, and 28.2% of glioma cases, respectively. The expression of LC3B and SQSTM1/p62 was notably higher in HGGs compared to LGGs. VPS34 exhibited a significant differential expression, displaying increased fold change in HGGs compared to LGGs. Additionally, it exhibited robust positive associations with Beclin1 (rs = 0.768), UVRAG (rs = 0.802), and ULK2 (rs = 0.786) in HGGs. This underscores a potential association between autophagy and the progression of gliomas. We provide preliminary data for the functional analysis of autophagy using a cell culture model and to identify potential targets for therapeutic interventions.

Advancing In Situ Food Monitoring through a Smart Lab-in-a-Package System Demonstrated by the Detection of Salmonella in Whole Chicken.

With food production shifting away from traditional farm-to-table approaches to efficient multistep supply chains, the incidence of food contamination has increased. Consequently, pathogen testing via inefficient culture-based methods has increased, despite its lack of real-time capabilities and need for centralized facilities. While in situ pathogen detection would address these limitations and enable individual product monitoring, accurate detection within unprocessed, packaged food products without user manipulation has proven elusive. Herein, "Lab-in-a-Package" is presented, a platform capable of sampling, concentrating, and detecting target pathogens within closed food packaging, without intervention. This system consists of a newly designed packaging tray and reagent-infused membrane that can be paired universally with diverse pathogen sensors. The inclined food packaging tray maximizes fluid localization onto the sensing interface, while the membrane acts as a reagent-immobilizing matrix and an antifouling barrier for the sensor. The platform is substantiated using a newly discovered Salmonella-responsive nucleic acid probe, which enables hands-free detection of 103 colony forming units (CFU) g-1 target pathogen in a packaged whole chicken. The platform remains effective when contamination is introduced with toolsand surfaces, ensuring widespread efficacy. Its real-world use for in situ detection is simulated using a handheld fluorescence scanner with smartphone connectivity.

The rise of diarrheal illnesses in the children of Pakistan amidst COVID-19: A narrative review.

Background: In Pakistan, 74 children out of 1000 lose their lives annually due to diarrheal illness. This commentary addresses the contributing factors aggravating this growing dilemma and the effect of a simultaneous rise in COVID-19 cases in a healthcare system ready to collapse, along with providing recommendations to alleviate the problems causing this spike in diarrheal cases. Methods: This narrative review has emphasized the causes of the spike in pediatric diarrheal illnesses in Pakistan as well as recommendations offered to lessen the burden by incorporating recent literature (n = 68). Tactics to tackle COVID-19 alongside diarrheal illnesses were also included. Pakistan was chosen to be assessed due to its high burden of child and infant mortality due to preventable causes. Results: The provision of safe drinking water, the proper use of Integrated Management of Newborn and Childhood Illnesses (IMNCI), adequate awareness of the benefits of breastfeeding, the use of correct rehydration techniques such as Oral Rehydration Therapy, and the crucial implementation of the EPI vaccination schedule can curb this increase in diarrheal cases. Conclusion: The increased prevalence of diarrheal diseases amongst the pediatric population of Pakistan can be attributed largely due to unsanitary drinking water. Emphasis must be put in the provision of safe drinking water. During the first years of life, children can be kept safe from deadly pathogens just by adequate breastfeeding. IMNCI and EPI must also be properly implemented.

Water sanitation in Karachi and its impact on health.

Karachi is the largest city and premiere industrial and financial center of Pakistan yet is subjected to major infrastructure deficits. Of primary concern is poor water sanitation which has predisposed a weak healthcare system and its citizens to increased infectious diseases. In Karachi, causes of this include a mismanaged sewage system, poor urban planning, and overcrowding. Several reasons such as lack of funding, corruption, and mismanagement have exacerbated circumstances placing extra strain on Karachi's already scarce water supply. In addition, lack of maintenance and regulation of the existing system has led to increased contaminated water delivery to citizens. Consequently, outbreaks of various water borne diseases such as typhoid, helicobacter pylori, malaria, diarrhea etc have severely impacted healthcare of citizens, especially with the COVID-19 pandemic. The situation is worsened by Karachi's rapidly growing population and lack of awareness among citizens regarding safe drinking water. Prior socioeconomic disparities, and illiteracy complicate access to medications and appropriate healthcare services. However, despite weak efforts from the government, several national and international organizations continue to strive to improve access to clean, drinkable water.

Probing the Synergistic Effect of Antibacterial Drug and Oleic Acid in Lipid-based Gastroretentive Matrices by Melt Molding Method.

INTRODUCTION: Clarithromycin (antibiotic), due to its narrow absorption window in the gastrointestinal tract, was taken as a model drug. MATERIALS AND METHODS: Focusing on the efficient drug delivery system, floating tablets that remain buoyant over gastric fluid for 24 hrs were produced by adopting the melt mold method using beeswax, gelucire, and oleic acid. To modulate the release pattern, a different concentration of 48/16 of beeswax and gelucire was used. RESULTS: To evaluate and characterize the final product, several tests, including the percentage recovery, in-vitro release studies, clarithromycin loading, scanning electron microscopy, differential scanning calorimeter, X-ray powder diffractometry, fourier transform infrared spectroscopy, weight variation, hardness, and friability, were carried out. Regarding the results, the encapsulation efficiency of the floating tablets was 39.5% to 59%, having weight variation with and without gelucire as 48/16 0.09525±0.0032g, and 0.09527±0.00286g to 0.0957±0.00321g, respectively. Clarithromycin release was controlled by using hydrophobic beeswax and hydrophilic gelucire 48/16. X-ray powder diffractometry, differential scanning calorimeter, and fourier transform infrared spectroscopy confirmed the absence of drug-polymer interaction, and exhibited amorphous and crystalline form of the drug after encapsulation. Drug release kinetics was determined by applying different models, such as zero-order, first-order model, Higuchi, and Korsemeyer-Pappas model. All formulations followed the Korsmeyer- Peppas model at 1.2 pH. CONCLUSION: Gastroretentive drug delivery systems were produced by using melt molding technique. In vitro dissolution represents the sustained release of the drug from the formulation.

Hypovitaminosis D in Hepatitis C patients and its relation with demographic and laboratory data.

OBJECTIVE: To determine the frequency of vitamin-D deficiency in hepatitis C patients and its relation with demographic and baseline laboratory data. METHODS: The cross-sectional study was conducted at the University Institute of Medical Laboratory Technology, Faculty of Allied Health Sciences, The University of Lahore, Pakistan, from April 3 to July 24, 2017, and comprised diagnosed hepatitis C genotype 3 patients aged 18-60 years. Demographic data was collected on a predesigned proforma. Tests included complete blood counts, liver function test, hepatitis C viral load and 25-hydroxy Vitamin-D level. Data was analysed using SPSS 24. RESULTS: Of the 115 patients, 54(47%) were male and 61(53%) were females. Mean vitamin-D level was 22.3±11.3. Total 25(21.7%) patients showed normal level of vitamin-D while the level was low in 90(78.3%) patients; 41(35.6%) showed vitamin-D insufficiency and 49(42.6%) vitamin-D deficiency. Significant effect of sun exposure was recorded on patient's vitamin-D level (p=0.00). Significantly low hepatitis C viral load was seen in patients with normal vitamin-D (p= 0. 02 6 ). CONCLUSIONS: Patients with hepatitis C virus infection had high incidence of hypo-vitaminosis D.

Deleterious Variants in WNT10A, EDAR, and EDA Causing Isolated and Syndromic Tooth Agenesis: A Structural Perspective from Molecular Dynamics Simulations.

The dental abnormalities are the typical features of many ectodermal dysplasias along with congenital malformations of nails, skin, hair, and sweat glands. However, several reports of non-syndromic/isolated tooth agenesis have also been found in the literature. The characteristic features of hypohidrotic ectodermal dysplasia (HED) comprise of hypodontia/oligodontia, along with hypohidrosis/anhidrosis, and hypotrichosis. Pathogenic variants in EDA, EDAR, EDARADD, and TRAF6, cause the phenotypic expression of HED. Genetic alterations in EDA and WNT10A cause particularly non-syndromic/isolated oligodontia. In the current project, we recruited 57 patients of 17 genetic pedigrees (A-Q) from different geographic regions of the world, including Pakistan, Egypt, Saudi Arabia, and Syria. The molecular investigation of different syndromic and non-syndromic dental conditions, including hypodontia, oligodontia, generalized odontodysplasia, and dental crowding was carried out by using exome and Sanger sequencing. We have identified a novel missense variant (c.311G>A; p.Arg104His) in WNT10A in three oligodontia patients of family A, two novel sequence variants (c.207delinsTT, p.Gly70Trpfs*25 and c.1300T>G; p.Try434Gly) in EDAR in three patients of family B and four patients of family C, respectively. To better understand the structural and functional consequences of missense variants in WNT10A and EDAR on the stability of the proteins, we have performed extensive molecular dynamic (MD) simulations. We have also identified three previously reported pathogenic variants (c.1076T>C; p.Met359Thr), (c.1133C>T; p.Thr378Met) and (c.594_595insC; Gly201Argfs*39) in EDA in family D (four patients), E (two patients) and F (one patient), correspondingly. Presently, our data explain the genetic cause of 18 syndromic and non-syndromic tooth agenesis patients in six autosomal recessive and X-linked pedigrees (A-F), which expand the mutational spectrum of these unique clinical manifestations.

Revealing quinquennial anticancer journey of morpholine: A SAR based review.

Morpholine, a six-membered heterocycle containing one nitrogen and one oxygen atom, is a moiety of great significance. It forms an important intermediate in many industrial and organic syntheses. Morpholine containing drugs are of high therapeutic value. Its wide array of pharmacological activity includes anti-diabetic, anti-emetic, growth stimulant, anti-depressant, bronchodilator and anticancer. Multi-drug resistance in cancer cases have emerged in the last few years and have led to the failure of many chemotherapeutic drugs. Newer treatment methods and drugs are being developed to overcome this problem. Target based drug discovery is an effective method to develop novel anticancer drugs. To develop newer drugs, previously reported work needs to be studied. Keeping this in mind, last five year's literature on morpholine used as anticancer agents has been reviewed and summarized in the paper herein.