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Ajwain (Trachyspermum ammi) belongs to the family Umbelliferae, is commonly used in traditional, and folk medicine due to its carminative, stimulant, antiseptic, diuretic, antihypertensive, and hepatoprotective activities. Non-specific lipid transfer proteins (nsLTPs) reported from various plants are known to be involved in transferring lipids between membranes and in plants defense response. Here, we describe the complete primary structure of a monomeric non-specific lipid transfer protein 1 (nsLTP1), with molecular weight of 9.66 kDa, from ajwain seeds. The nsLTP1 has been purified by combination of chromatographic techniques, and further characterized by mass spectrometry, and Edman degradation. The ajwain nsLTP1 is comprised of 91 amino acids, with eight conserved cysteine residues. The amino acid sequence based predicted three dimensional (3D) structure is composed of four α-helices stabilized by four disulfide bonds, and a long C -terminal tail. The predicted model was verified by using different computational tools; i.e. ERRAT, verify 3D web server, and PROCHECK. The docking of ajwain nsLTP1 with ligands; myristic acid (MYR), and oleic acid (OLE) was performed, and molecular dynamics (MD) simulation was used to validate the docking results. The findings suggested that amino acids; Leu11, Leu12, Ala55, Ala56, Val15, Tyr59, and Leu62 are pivotal for the binding of lipid molecules with ajwain nsLTP1.

Background Oral cancer is considered a major public health problem due to its high mortality and morbidity rates. Survival rate of OSCC can be significantly improved by using non-invasive tool such as salivary biomarkers for detection of OSCC which is considered a promising approach. Cathepsin B is a lysosomal cysteine protease, present in abundant quantities in lysosome of cells, tissues and different biological fluids. Increased expression of Cathepsin B was observed in many malignancies including oral cancer. The present study was designed to determine the salivary levels of Cathepsin B in different histological grades of OSCC. Method In this study, total no. of 80 research participants were enrolled which were divided into four groups. Each group comprised 20 participants, group 1 comprised 20 patients of OSCC (well differentiated), group 2 comprised 20 patients of OSCC (moderately differentiated), group 3 comprised 20 patients of OSCC (poorly differentiated) and group 4 comprised 20 healthy controls. Saliva sample was collected from all the four study groups and salivary Cathepsin B levels were analyzed by ELISA sandwich technique in duplicate. Results Salivary levels of Cathepsin B were significantly increased with p value (< 0.001) in patients of OSCC as compared to control group according to both histological grades and tumor size. Highest mean Cathepsin B levels in well differentiated OSCC followed by poorly differentiated OSCC and moderately differentiated OSCC were observed. Conclusion Results of the present study suggests that Cathepsin B has a great value as a salivary biomarker for diagnosis and monitoring of OSCC in different histological grades. This will further lead to increase survival rate and improve the prognosis of OSCC.

Snake envenomation affects millions of people worldwide especially rural population in developing countries. High production cost, poor accessibility and side-effects associated with antivenom treatment call for newer approaches. Nanoparticles could provide alternative therapy due to their biocompatibility, ease of production and stability. In this study, Titanium (IV) isopropoxide was reduced to make TiO 2 nanoparticles by chemical and green synthesis method utilizing potato peels and neem leaves extract. The synthesized particles were characterized by Scanning Electron Microscope, Electron Dispersive X-ray Spectroscopy and Fourier Transform Infrared Spectroscopy. The synthesized nanoparticles are spherical in shape with sizes ranging from 41–64 nm and molecules, such as polyphenols, flavonoids, and alkaloids in plant extracts act as reducing and capping agents. The nanoparticles were evaluated for in vitro venom neutralization assays against the Naja naja venom. The hemocompatibility assay showed that the TiO 2 NPs are non-toxic, indicating their safe use. The TiO 2 NPs were able to significantly inhibit venom induced hemolysis of RBCs and blood anticoagulation effect ( p -values ≤0.000). Overall, the study suggests that TiO 2 NPs could be effective in reducing the toxicity of Naja naja venom, providing a practical and cost-effective therapeutic option to be used as alternative treatments for snake envenomation.

Dental caries is a multifactorial disease mainly caused by cariogenic bacteria commonly found in the oral cavity. Dental caries may cause demineralization of the tooth, cavitation, hypersensitivity, pulp inflammation, and even tooth loss if left untreated. Saliva secreted in the oral cavity can serve as a tool for identification of biomarkers for early detection of diseases. In the present study, differential expression of salivary proteins from 33 dental caries patients was compared with 10 control subjects. The unstimulated saliva was analyzed by 12% SDS-PAGE and two-dimensional gel electrophoresis. Gelatin and casein zymography was performed to check for protease activity. Also, salivary IgAs from both groups were compared by sandwich ELISA technique. Dental caries patient’s saliva showed decreased caseinolytic and increased gelatinolytic activity probably due to metalloproteases and cathepsins. Mean salivary levels of sIgA were also significantly higher (p<0.018) in dental caries saliva samples. The 2D electrophoresis profile of both the groups showed regions on gel with visually detectable alterations in protein expression. The present study is among the few initial studies in the locality for identification of protein differences in saliva from dental caries patients and has demonstrated a good potential to identify alterations. However, a large population-based analysis is required to validate these findings to be translated as a tool for indicative applications.

To effectively counter the evolving threat of SARS-CoV-2 variants, modifications and/or redesigning of mRNA vaccine construct are essentially required. Herein, the design and immunoinformatic assessment of a candidate novel mRNA vaccine construct, DOW-21, are discussed. Briefly, immunologically important domains, N-terminal domain (NTD) and receptor binding domain (RBD), of the spike protein of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) were assessed for sequence, structure, and epitope variations. Based on the assessment, a novel hypothetical NTD (h-NTD) and RBD (h-RBD) were designed to hold all overlapping immune escape variations. The construct sequence was then developed, where h-NTD and h-RBD were intervened by 10-mer gly-ala repeat and the terminals were flanked by regulatory sequences for better intracellular transportation and expression of the coding regions. The protein encoded by the construct holds structural attributes (RMSD NTD: 0.42 Å; RMSD RBD: 0.15 Å) found in the respective domains of SARS-CoV-2 immune escape variants. In addition, it provides coverage to the immunogenic sites of the respective domains found in SARS-CoV-2 variants. Later, the nucleotide sequence of the construct was optimized for GC ratio (56%) and microRNA binding sites to ensure smooth translation. Post-injection antibody titer was also predicted (~12000 AU) to be robust. In summary, the construct proposed in this study could potentially provide broad spectrum coverage in relation to SARS-CoV-2 immune escape variants.

The amino acid sequence of β I -globin chain from Sindhi Krait ( Bungarus sindanus sindanus) was determined to study the molecular evolution among snakes. The hemoglobin was isolated from the red blood cells and was analyzed by ion-exchange chromatography (IEX). The crude globin was subjected to reversed phased-high performance liquid chromatography (RP-HPLC) using C4 column. The N-terminal sequences of intact globin chains and tryptic peptides were determined by Edman degradation in a pulsed liquid gas phase sequencer using an online Phenylthiohydantoin analyzer. Sindhi Krait is expected to express three hemoglobin components that are composed of β II , β I , α D and α A -globin chains, as apparent by IEX, RP-HPLC and N-terminal sequence analyses. Sequence alignment and phylogenetic analyses of β I globin chain from Sindhi Krait showed closest relationship with β I globin chain from Rattlesnake, Water snake and Indigo snake. Interestingly, comparison of primary sequence of β I globin chain of Sindhi Krait with human β chain revealed 63 % similarity along with the retention of all heme contact points. Variations among the two sequences were prominent at αβ contact points and in regions directly not important for function.

The amino acid sequence of [beta]I-globin chain from Sindhi Krait (Bungarus sindanus sindanus) was determined to study the molecular evolution among snakes. The hemoglobin was isolated from the red blood cells and was analyzed by ion-exchange chromatography (IEX). The crude globin was subjected to reversed phased-high performance liquid chromatography (RP-HPLC) using C4 column. The N-terminal sequences of intact globin chains and tryptic peptides were determined by Edman degradation in a pulsed liquid gas phase sequencer using an online Phenylthiohydantoin analyzer. Sindhi Krait is expected to express three hemoglobin components that are composed of [beta]II, [beta]I, [alpha]D and [alpha]A-globin chains, as apparent by IEX, RP-HPLC and N-terminal sequence analyses. Sequence alignment and phylogenetic analyses of [beta]I globin chain from Sindhi Krait showed closest relationship with [beta]I globin chain from Rattlesnake, Water snake and Indigo snake. Interestingly, comparison of primary sequence of [beta]I globin chain of Sindhi Krait with human [beta] chain revealed 63 % similarity along with the retention of all heme contact points. Variations among the two sequences were prominent at [alpha][beta] contact points and in regions directly not important for function.

The amino acid sequence of beta super(I)-globin chain from Sindhi Krait (Bungarus sindanus sindanus) was determined to study the molecular evolution among snakes. The hemoglobin was isolated from the red blood cells and was analyzed by ion-exchange chromatography (IEX). The crude globin was subjected to reversed phased-high performance liquid chromatography (RP-HPLC) using C4 column. The N-terminal sequences of intact globin chains and tryptic peptides were determined by Edman degradation in a pulsed liquid gas phase sequencer using an online Phenylthiohydantoin analyzer. Sindhi Krait is expected to express three hemoglobin components that are composed of beta super(II), beta super(I), alpha super(D) and alpha super(A)-globin chains, as apparent by IEX, RP-HPLC and N-terminal sequence analyses. Sequence alignment and phylogenetic analyses of beta super(I) globin chain from Sindhi Krait showed closest relationship with beta super(I) globin chain from Rattlesnake, Water snake and Indigo snake. Interestingly, comparison of primary sequence of beta super(I) globin chain of Sindhi Krait with human beta chain revealed 63 % similarity along with the retention of all heme contact points. Variations among the two sequences were prominent at alpha beta contact points and in regions directly not important for function.

Using artificial intelligence (AI) to enhance chimeric antigen receptor (CAR)-based therapies’ design, production, and delivery is a novel and promising approach. This review provides an overview of the current applications and challenges of AI for CAR-based therapies and suggests some directions for future research and development. This paper examines some of the recent advances of AI for CAR-based therapies, for example, using deep learning (DL) to design CARs that target multiple antigens and avoid antigen escape; using natural language processing to extract relevant information from clinical reports and literature; using computer vision to analyze the morphology and phenotype of CAR cells; using reinforcement learning to optimize the dose and schedule of CAR infusion; and using AI to predict the efficacy and toxicity of CAR-based therapies. These applications demonstrate the potential of AI to improve the quality and efficiency of CAR-based therapies and to provide personalized and precise treatments for cancer patients. However, there are also some challenges and limitations of using AI for CAR-based therapies, for example, the lack of high-quality and standardized data; the need for validation and verification of AI models; the risk of bias and error in AI outputs; the ethical, legal, and social issues of using AI for health care; and the possible impact of AI on the human role and responsibility in cancer immunotherapy. It is important to establish a multidisciplinary collaboration among researchers, clinicians, regulators, and patients to address these challenges and to ensure the safe and responsible use of AI for CAR-based therapies. Graphical abstract

Objective: To describe bacteriological profile, morbidity and mortality of acute bacterial meningitis (ABM) in children and to compare these parameters before and after the introduction of Pneumococcal vaccine in Pakistan National Immunization Program.Methods: The present descriptive study was conducted at the Department of Paediatric Medicine of The Children