Implementation of Next-Generation Sequencing in Saudi Arabia for HER2-Positive Breast Cancer

Breast cancer is a common malignancy that poses a hazard to women's health. In 2021, around 2.3 million new cases are predicted to be discovered, with a mortality rate of 6.9% on average. Breast cancer accounts for 14.8% of malignancies among the Saudis with an 8.5% fatality rate. Breast cancers that are HER2 positive account for 15 to 20% of all breast cancers. We intended to investigate the genetic mutations and the clinicopathological aspects of HER2 positive breast cancer patients. We used TruSight Tumor 15 using Next-Generation Sequencing (NGS) to look at genetic changes in 126 Saudi women with stage I to IV breast cancer. c-MET (p = 0.001), c-KIT (p = 0.001), and PIK3CA (p = 0.0001), were shown to be substantially linked with HER2 positive patients. We also detected mutations in other genes, including BRAF, EGFR, and KRAS. Tumor size, grade, stage, and nodal status were all associated with increased levels of HER2 expression. Our results recommend that patients with HER2 positive breast cancer in Saudi Arabia have a high mutational burden, which may be related to trastuzumab resistance. We expect that in the future, targeting these mutations will be a promising therapeutic method for the treatment of breast cancer.     

Wheat-yellow pumpkin composite flour: Physico-functional,rheological, antioxidant potential and quality properties of pan and flat bread

The impact of yellow pumpkin powder (YP) substitution (5, 10, and 15%) on wheat flour's physico-functional, pasting, gel texture, and dough rheology was studied. Moreover, the nutritional, organoleptic properties and bioactivity of the composite pan and pita bread were evaluated. An improved water holding capacity was noticed for the blended flour than for control. The pasting parameters were declined significantly (p < 0.05) with increasing YP. Composite flours presented a softer gel texture in the presence of YP. Reduced water absorption, increased dough development time, and lower stability for combined flour dough. The bread with YP depicted increased protein, fat, fiber, and mineral contents, while a reduced volume and specific volume were noticed for pan bread. YP incorporated 5% and did not compromise pan and pita bread's color and overall acceptability. Additionally, composite bread depicted higher total phenolics with enhanced antioxidant activities at the higher substitution of YP.     

Plant lectins as potent Anti-coronaviruses,Anti-inflammatory,antinociceptive and antiulcer agents

Lectins are defined as carbohydrate-binding proteins/glycoproteins of none immune origin, they are ubiquitous in nature, exist from bacteria to human cells. And due to their carbohydrate-binding recognition capacity, they have been a useful biological tool for the purification of glycoproteins and their subsequent characterization. Some plant lectins have also been revealed to own antinociceptive, antiulcer, and anti-inflammatory properties, where these features, in many instances, depending on the lectin carbohydrate-binding site. Coronavirus disease of 2019 (COVID-19) is a respiratory disease that struck the entire world leaving millions of people dead and more infected. Although COVID-19 vaccines have been made available, and quite a large number of world populations have already been immunized, the viral infection rates remained in acceleration, which continues to provoke major concern about the vaccines' efficacy. The belief in the ineffectiveness of the vaccine has been attributed in part to the recurrent mutations that occur in the epitope determinant fragments of the virus. Coronavirus envelope surface is extensively glycosylated being covered by more than sixty N-linked oligomannose, composite, and hybrid glycans with a core of Man3GlcNAc2Asn. In addition some O–linked glycans are also detected. Of these glyco-chains, many have also been exposed to several mutations, and a few remained conserved. Therefore, numerous plant lectins with a specificity directed towards these viral envelope sugars have been found to interact preferentially with them and are suggested to be scrutinized as a possible future tool to combat coronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through blocking the viral attachment to the host cells. In this review, we will discuss the possible applications of plant lectins as anti-coronaviruses including SARS-CoV-2, antinociceptive, anti-inflammatory, and antiulcer agents with the proposed mechanism of their actions.     

Cytoplasmic domain and enzymatic activity of ACE2 are not required for PI4KB dependent endocytosis entry of SARS-CoV-2 into host cells

The recent COVID-19 pandemic poses a global health emergency. Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor-human angiotensin converting enzyme 2 (ACE2). Here, by using lentivirus based pseudotypes bearing spike protein, we demonstrated that entry of SARS-CoV-2 into host cells was dependent on clathrin-mediated endocytosis, and phosphoinositides played essential roles during this process. In addition, we showed that the intracellular domain and the catalytic activity of ACE2 were not required for efficient virus entry. Finally, we showed that the current predominant Delta variant, although with high infectivity and high syncytium formation, also entered cells through clathrin-mediated endocytosis. These results provide new insights into SARS-CoV-2 cellular entry and present proof of principle that targeting viral entry could be an effective way to treat different variant infections.     

Effect of diet and starvation on the activity state of branched-chain 2-oxo-acid dehydrogenase complex in rat liver and heart

In rats fed a high-protein diet, the branched-chain 2-oxo-acid dehydrogenase complex in liver was essentially fully acitve and its activity state was unaffected by subsequent starvation for 48 h. Feeding with a low-protein diet led to a decrease in the activity state which was essentially reversed by 48 h of starvation. In heart, the enzyme was primarily inactive (activity state 18%) in rats fed a high-protein diet, with both low-protein diet and starvation leading to a further decrease in the activity state.     

Integrated computational approaches to screen gene expression data to determine key genes and therapeutic targets for type-2 diabetes mellitus

There is a rapid rise in cases of Type-2-diabetes mellitus (T2DM) globally, irrespective of the geography, ethnicity or any other variable factors. The molecular mechanisms that could cause the condition of T2DM need to be more thoroughly analysed to understand the clinical manifestations and to derive better therapeutic regimes. Tools in bioinformatics are used to trace out key gene elements and to identify the key causative gene elements and their possible therapeutic agents. Microarray datasets were retrieved from the Gene expression omnibus database and studied using R to derive different expressed gene (DEG) elements. With the comparison of the expressed genes with disease specific genes in DisGeNET, the final annotated genes were taken for analysis. Gene Ontology studies, Protein–protein interaction (PPI), Co-expression analysis, Gene-drug interactions were performed to scale down the hub genes and to identify the novelty across the genes analysed so far. In vivo and invitro analysis of key genes and the trace of interaction pathway is crucial to better understand the unique outcomes from the novel genes, forming the basis to understand the pathway that ends up causing T2DM. Afterwards, docking was executed enabling recognition of interacting residues involved in inhibition. The complex CCL5-265 and CD8A-40585 thus docked showed best results as is evident from its PCA analysis and MMGBSA calculation. There is now scope for deriving candidate drugs that could possibly detect personalized therapies for T2DM.     

Regulatory and molecular properties of citrate synthases from methylotrophs

Abstract Gram-negative methylotrophs contain a high- M _r'large' citrate synthase. Gram-positive methylotrophs, on the other hand, contain a 'small' citrate synthase. These differences in M _r coincided partly with differences in NADH sensitivity. Citrate synthases from obligate Gram-negative and Gram-positive facultative methylotrophs were insensitive to feedback inhibition by NADH; only the enzymes from Gram-negative facultative methylotrophs were inhibited by NADH.     

The acetyl-CoA pathway of autotrophic growth

Abstract The most direct conceivable route for synthesis of multicarbon compounds from CO₂ is to join two molecules of CO₂ together to make a 2-carbon compound and then polymerize the 2-carbon compound or add CO₂ successively to the 2-carbon compound to make multicarbon compounds. Recently, it has been demonstrated that the bacterium, Clostridium thermoaceticum , grows autotrophically by such a process. The mechanism involves the reduction of one molecule of CO₂ to a methyl group and then its combination with a second molecule of CO₂ and CoA to form acetyl-CoA. We have designated this autotrophic pathway the acetyl-CoA pathway [1]. Evidence is accumulating that this pathway is utilized by other bacteria that grow with CO₂ and H₂ as the source of carbon and energy. This group includes bacteria which, like C. thermoaceticum , produce acetate as a major end product and are called acetogens or acetogenic bacteria. It also includes the methane-producing bacteria and sulfate-reducing bacteria.
The purpose of this review is to examine critically the evidence that the acetyl-CoA pathway occurs in other bacteria by a mechanism that is the same or similar to that found in C. thermoaceticum . For this purpose, the mechanism of the acetyl-CoA pathway, as found in C. thermoaceticum , is described and hypothetical mechanisms for other organisms are presented based on the acetyl-CoA pathway of C. thermoaceticum . The available data have been reviewed to determine if the hypothetical schemes are in accord with presently known facts. We conclude that the formation of acetyl-CoA by other acetogens, the methanogens and sulphate-reducing bacteria occurs by a mechanism very similar to that of C. thermoaceticum .     

Identification of a novel adhesion molecule in human leukocytes by monoclonal antibody LB-2

Monoclonal antibody LB-2 to a surface antigen on human B cells, lymphoblast, monocytes and vascular endothelial cells largely inhibited adhesion among Epstein Barr virus-immortalized normal B cells (EBV-B) and concanavalin A-stimulated blood mononuclear cells (Con A-BMC) before and after phorbol ester treatment. The antibody inhibited to a lesser extent phorbol ester-induced aggregation of monocytes, U937 cells and fresh BMC and had virtually no inhibitory effect on the adhesion among enriched T cells and granulocytes. A surface glycoprotein band of 84 kDa was obtained from EBV-B cells by immunoprecipitation and gel electrophoresis. Immunological and biochemical studies clearly distinguished this molecule from gp90 and associated glycoproteins which also mediate leukocyte adhesion.     

开放式空气二氧化碳浓度增高对小麦氮素吸收利用的影响

2001—2003年,利用我国唯一的农田开放式空气CO₂浓度增高 (free-air carbon dioxide enrichment,FACE) 技术平台,研究了FACE条件下冬小麦宁麦9号不同生育期N含量、吸收、分配和N效率的响应.结果表明：与对照相比,FACE处理使不同生育时期植株含N率显著降低,降幅达4.4%～13.4%;不同生育时期吸N量显著增加(7.4%～25.4%),生育中期的增幅明显大于生育前、后期;不同生育时期茎鞘的N积累能力相对增强,叶片N积累能力相对减弱,而对麦穗N积累能力的影响因生育进程而异;FACE处理使小麦不同生育时期N物质生产效率(5.5%～10.3%)、成熟期N收获指数(16.3%)和N籽粒生产效率(9.3%)均显著或极显著增加;增施N肥,使小麦不同生育时期N含量和吸收量呈增加趋势,使N效率呈下降趋势,而对N在各器官中分配的影响较小.