Ethnomedicines’ effects on the process of vascularisation in embryonated chicken eggs

731-738Angiogenesis (vascularisation) is a vivacious progression during embryonic development, which is required for the growth, development, wound healing and maintenance. However, the process may turn into pathological conditions; excessive angiogenesis occurs in diseases such as cancer, diabetic blindness, age related macular degeneration, rheumatoid arthritis, etc., whereas insufficient angiogenesis occurs in diseases like coronary artery disease and chronic wounds. Since ancient times, the human population has been dependent on plants for deriving medicines to cure diseases. In the present study, aqueous extract of 04 ethnomedicinal plants parts, Butea monosperma (Kamarkas), Dioscorea hispida (Beychandi), Myristica fragrans (Nutmeg) and Mesua ferrea (Nagkesar), were evaluated for modulation of angiogenesis in chorioallantoic membrane (CAM) of embryonated chicken eggs. Out of these 04, B. monosperma revealed mild inhibitory effects on angiogenesis. M. fragrans and D. hispida inhibited angiogenesis, but also showed detrimental effect on growth of normal CAM with irregular outgrowths in form of projections and uneven thickness. The M. ferrea revealed its potential as antiangiogenic material by inhibiting the vascularisation by reducing the number of blood vessels without effecting normal morphology of CAM tissue. The study paves way to screen ethnomedicinal wealth for screening of plant produce for therapeutic purposes in ameliorating angiogenic disorders

Insights into synonymous codon usage bias in hepatitis c virus and Its adaptation to hosts

© 2023 by the authors. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/. This document is the Published version of a Published Work that appeared in final form in Pathogens. To access the final edited and published work see https://doi.org/10.3390/pathogens12020325Hepatitis C virus (HCV) is enveloped RNA virus, encoding for a polyprotein that is processed by cellular proteases. The virus is responsible for liver cirrhosis, allograft rejection, and human hepatocellular carcinoma. Based on studies including compositional analysis, odds ratio analysis, parity analysis, skew analysis, relative synonymous codon usage, codon bias, and protein properties, it was evident that codon usage bias in HCV is dependent upon the nucleotide composition. Codon context analysis revealed CTC-CTG as a preferred codon pair. While CGA and CGT codons were rare, none of the codons were rare in HCV-like viruses envisaged in the present study. Many of the preferred codon pairs were valine amino acid-initiated, which possibly infers viral infectivity; hence the role of selection forces appears to act on the HCV genome, which was further validated by neutrality analysis where selection accounted for 87.28%, while mutation accounted for 12.72% force shaping codon usage. Furthermore, codon usage was correlated with the length of the genome. HCV viruses prefer valine-initiated codon pairs, while HCV-like viruses prefer alanine-initiated codon pairs. The HCV host range is very narrow and is confined to only humans and chimpanzees. Based on indices including codon usage correlation analysis, similarity index, and relative codon deoptimization index, it is evident in the study that the chimpanzee is the primary host of the virus. The present study helped elucidate the preferred host for HCV. The information presented in the study paved the way for generating an attenuated vaccine candidate through viral recoding, with finely tuned nucleotide composition and a perfect balance of preferred and rare codons

Colistin the last resort drug in 21st century antibiotics to combat Multidrug resistance superbugs

Polymyxin' E' (Colistin) is considered the last resort therapy against Multidrug resistance (MDR) bacteria, mainly Klebsiella peumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli and play a critical role in causing life-threatening infection, and their prevalence is increasing as a big concern globally. Apart from immunological adaptation, chromosomal mutations and plasmid-mediated genes are mostly associated with this resistance at the molecular level. Therefore, the current review extensively focused on Colistin as a drug in 21st-century antibiotics, the activities spectrum with diverse resistance mechanisms of bacteria against Colistin, and emerging approaches of Colistin from discovery to tackling MDR. In the study, we got to know about the challenges and new developments with old weapons like phage therapy as well as new approaches like Phage display and drug repurposing, in addition to the chromosomal and plasmid-mediated genes that play a role in antimicrobial resistance (AMR). The present study would provide insight into the prognostic aspect of combating MDR

Ethnomedicines’ effects on the process of vascularisation in embryonated chicken eggs

Angiogenesis (vascularisation) is a vivacious progression during embryonic development, which is required for the growth, development, wound healing and maintenance. However, the process may turn into pathological conditions; excessive angiogenesis occurs in diseases such as cancer, diabetic blindness, age related macular degeneration, rheumatoid arthritis, etc., whereas insufficient angiogenesis occurs in diseases like coronary artery disease and chronic wounds. Since ancient times, the human population has been dependent on plants for deriving medicines to cure diseases. In the present study, aqueous extract of 04 ethnomedicinal plants parts, Butea monosperma (Kamarkas), Dioscorea hispida (Beychandi), Myristica fragrans (Nutmeg) and Mesua ferrea (Nagkesar), were evaluated for modulation of angiogenesis in chorioallantoic membrane (CAM) of embryonated chicken eggs. Out of these 04, B. monosperma revealed mild inhibitory effects on angiogenesis. M. fragrans and D. hispida inhibited angiogenesis, but also showed detrimental effect on growth of normal CAM with irregular outgrowths in form of projections and uneven thickness. The M. ferrea revealed its potential as antiangiogenic material by inhibiting the vascularisation by reducing the number of blood vessels without effecting normal morphology of CAM tissue. The study paves way to screen ethnomedicinal wealth for screening of plant produce for therapeutic purposes in ameliorating angiogenic disorders

Anti-Proliferative Role of Recombinant Lethal Toxin of Bacillus Anthracis on Primary Mammary Ductal Carcinoma Cells Revealing Its Therapeutic Potential

Bacillus anthracis secretes three secretary proteins; lethal factor (LF), protective antigen (PA) and edema factor (EF). The LF has ability to check proliferation of mammary tumors, chiefly depending on mitogen activated protein kinase (MAPK) signaling pathway. Evaluation of therapeutic potential of recombinant LF (rLF), recombinant PA (rPA) and lethal toxin (rLF + rPA = LeTx) on the primary mammary ductal carcinoma cells revealed significant (p \u3c 0.01) reduction in proliferation of tumor cells with mean inhibition indices of 28.0 ±1.37% and 19.6 ± 1.47% respectively. However, treatment with rPA alone had no significant anti-proliferative effect as evident by low mean inhibition index of 3.4 ± 3.87%. The higher inhibition index observed for rLF alone as compared to LeTx is contrary to the existing knowledge on LF, which explains the requirement of PA dependent endocytosis for its enzymatic activity. Therefore, the plausible existence of PA independent mode of action of LF including direct receptor mediated endocytosis or modulation of signal transduction cascade via unknown means is hypothesized. In silico protein docking analysis of other cellular receptors for any plausibility to play the role of receptor for LF revealed c-Met receptor showing strongest affinity for LF (H bond = 19; Free energy = -773.96), followed by nerve growth factor receptor (NGFR) and human epidermal growth factor receptor (HER)-1. The study summarizes the use of rLF or LeTx as therapeutic molecule against primary mammary ductal carcinoma cells and also the c-Met as potential alternative receptor for LF to mediate and modulate PA independent signal transduction

Terapan Iptek Kewirausahaan Untuk Hasil Produk Pengelasan Kepada Masyarakat Kayang Makmur, Kabupaten Madiun

Tingkat kemampuan berwirausaha dibidang pengelasan yang dimiliki masyarakat Dusun Kayang Makmur, Desa Bader, Kecamatan Dolopo, Kabupaten Madiun dinilai rendah  karena keterbatasan materi, hal ini berdampak pada perawatan dan perbaikan dalam bentuk pengelasan untuk alat pertanian dari baja yang sebagian besar digunakan oleh masyarakat Dusun Kayang Makmur. Oleh karena itu, diadakannya pelatihan pengelasan dan kewirausahaan yang kemudian hari dikembangkan menjadi suatu ide usaha. Dengan penguasaan keterampilan pengelasan maka produk yang dihasilkan masyarakat desa mampu dijadikan kegiatan berwirausaha dan bersaing pada pasar di era globalisasi. Penyelenggaraan kegiatan program kemitraan masyarakat ini dilaksanakan dengan beberapa parameter yang dapat dicapai luaran dari kegiatan ini berupa kemampuan kewirausahaan yang bermanfaat bagi masyarakat Dusun Kayang Makmur. Tahapan pelaksanaan terdiri dari teori dasar kewirausahaan dan praktek pemasaran produk yang telah dibuat. Hasil dari pengabdian (pelatihan) kewirausahaan berupa pengetahuan dalam hal dasar kewirausahaan dan penerapannya

Advances in Developing Therapies to Combat Zika Virus: Current Knowledge and Future Perspectives

Zika virus (ZIKV) remained largely quiescent for nearly six decades after its first appearance in 1947. ZIKV reappeared after 2007, resulting in a declaration of an international “public health emergency” in 2016 by the World Health Organization (WHO). Until this time, ZIKV was considered to induce only mild illness, but it has now been established as the cause of severe clinical manifestations, including fetal anomalies, neurological problems, and autoimmune disorders. Infection during pregnancy can cause congenital brain abnormalities, including microcephaly and neurological degeneration, and in other cases, Guillain-Barré syndrome, making infections with ZIKV a substantial public health concern. Genomic and molecular investigations are underway to investigate ZIKV pathology and its recent enhanced pathogenicity, as well as to design safe and potent vaccines, drugs, and therapeutics. This review describes progress in the design and development of various anti-ZIKV therapeutics, including drugs targeting virus entry into cells and the helicase protein, nucleosides, inhibitors of NS3 protein, small molecules, methyltransferase inhibitors, interferons, repurposed drugs, drugs designed with the aid of computers, neutralizing antibodies, convalescent serum, antibodies that limit antibody-dependent enhancement, and herbal medicines. Additionally, covalent inhibitors of viral protein expression and anti-Toll-like receptor molecules are discussed. To counter ZIKV-associated disease, we need to make rapid progress in developing novel therapies that work effectually to inhibit ZIKV

Ebola virus - Epidemiology, Diagnosis, and Control: Threat to Humans, Lessons Learnt, and Preparedness Plans - an Update on Its 40 Year\u27s Journey

Ebola virus (EBOV) is an extremely contagious pathogen and causes lethal hemorrhagic fever disease in man and animals. The recently occurred Ebola virus disease (EVD) outbreaks in the West African countries have categorized it as an international health concern. For the virus maintenance and transmission, the non-human primates and reservoir hosts like fruit bats have played a vital role. For curbing the disease timely, we need effective therapeutics/prophylactics, however, in the absence of any approved vaccine, timely diagnosis and monitoring of EBOV remains of utmost importance. The technologically advanced vaccines like a viral-vectored vaccine, DNA vaccine and virus-like particles are underway for testing against EBOV. In the absence of any effective control measure, the adaptation of high standards of biosecurity measures, strict sanitary and hygienic practices, strengthening of surveillance and monitoring systems, imposing appropriate quarantine checks and vigilance on trade, transport, and movement of visitors from EVD endemic countries remains the answer of choice for tackling the EBOV spread. Herein, we converse with the current scenario of EBOV giving due emphasis on animal and veterinary perspectives along with advances in diagnosis and control strategies to be adopted, lessons learned from the recent outbreaks and the global preparedness plans. To retrieve the evolutionary information, we have analyzed a total of 56 genome sequences of various EBOV species submitted between 1976 and 2016 in public databases

Application of codon usage and context analysis in genes up- or down-regulated in neurodegeneration and cancer to combat comorbidities

IntroductionNeurodegeneration and cancer present in comorbidities with inverse effects due to the expression of genes and pathways acting in opposition. Identifying and studying the genes simultaneously up or downregulated during morbidities helps curb both ailments together.MethodsThis study examines four genes. Three of these (Amyloid Beta Precursor Protein (APP), Cyclin D1 (CCND1), and Cyclin E2 (CCNE2) are upregulated, and one protein phosphatase 2 phosphatase activator (PTPA) is simultaneously downregulated in both disorders. We investigated molecular patterns, codon usage, codon usage bias, nucleotide bias in the third codon position, preferred codons, preferred codon pairs, rare codons, and codon context.ResultsParity analysis revealed that T is preferred over A, and G is preferred over C in the third codon position, suggesting composition plays no role in nucleotide bias in both the upregulated and downregulated gene sets and that mutational forces are stronger in upregulated gene sets than in downregulated ones. Transcript length influenced the overall %A composition and codon bias, and the codon AGG exerted the strongest influence on codon usage in both the upregulated and downregulated gene sets. Codons ending in G/C were preferred for 16 amino acids, and glutamic acid-, aspartic acid-, leucine-, valine-, and phenylalanine-initiated codon pairs were preferred in all genes. Codons CTA (Leu), GTA (Val), CAA (Gln), and CGT (Arg) were underrepresented in all examined genes.DiscussionUsing advanced gene editing tools such as CRISPR/Cas or any other gene augmentation technique, these recoded genes may be introduced into the human body to optimize gene expression levels to augment neurodegeneration and cancer therapeutic regimens simultaneously

Advances in Designing and Developing Vaccines, Drugs and Therapeutic Approaches to Counter Human Papilloma Virus

Human papillomavirus (HPV) is a viral infection with skin-to-skin based transmission mode. HPV annually caused over 500,000 cancer cases including cervical, anogenital and oropharyngeal cancer among others. HPV vaccination has become a public-health concern, worldwide, to prevent the cases of HPV infections including precancerous lesions, cervical cancers, and genital warts especially in adolescent female and male population by launching national programs with international alliances. Currently, available prophylactic and therapeutic vaccines are expensive to be used in developing countries for vaccination programs. The recent progress in immunotherapy, biotechnology, recombinant DNA technology and molecular biology along with alternative and complementary medicinal systems have paved novel ways and valuable opportunities to design and develop effective prophylactic and therapeutic vaccines, drugs and treatment approach to counter HPV effectively. Exploration and more researches on such advances could result in the gradual reduction in the incidences of HPV cases across the world. The present review presents a current global scenario and futuristic prospects of the advanced prophylactic and therapeutic approaches against HPV along with recent patents coverage of the progress and advances in drugs, vaccines and therapeutic regimens to effectively combat HPV infections and its cancerous conditions