Therapeutic compounds from medicinal plant endophytes: molecular and metabolic adaptations.

During the last few decades, endophytes have attracted increased attention due to their ability to produce a plethora of bioactive secondary metabolites. These compounds not only help the endophytes to outcompete other plant-associated microbes or pathogens through quorum sensing, but also enable them to surmount the plant immune system. However, only a very few studies have described the interlink between various biochemical and molecular factors of host-microbe interactions involved in the production of these pharmacological metabolites. The peculiar mechanisms by which endophytes modulate plant physiology and metabolism through elicitors, as well as how they use transitional compounds of primary and secondary metabolism as nutrients and precursors for the synthesis of new compounds or enhancing existing metabolites, are still less understood. This study thus attempts to address the aspects of synthesis of such metabolites used in therapeutics by the endophytes in the light of their ecological significance, adaptation, and intercommunity interactions. Our study explores how endophytes adapt to the specific host environment, especially in medicinal plants that produce metabolites with pharmacological potential and simultaneously modulate host gene expression for the biosynthesis of these metabolites. We also discuss the differential interactions of fungal and bacterial endophytes with their hosts.

Effect of fetal liver condition media derived cytokines(IL-6 and Flt-3) on human bone marrow stem cells colony formation.

Earlier research from our laboratory demonstrated the presence of stimulatory activity of different growth factors in the fetal liver (FL) extracts when collected in a medium known as fetal liver conditioned medium (FLCM) using Enzyme-linked Immunosorbent Assay (ELISA). In the present study, we have assessed two other cytokines viz. IL-6 and FMS like tyrosine kinase-3 (Flt-3) with the help of bioneutralization assay. FLCM was prepared by incubating fetal liver cells with Iscove's Modified Dulbecco's Medium (IMDM) containing 10% fetal bovine serum (FBS) and 10% Phytohemagglutinin and collected after 24hrs, 48hrs, 72 hrs. and on the 7th day of incubation. Clonal cultures were established for 1 X 105 normal bone marrow (BM) mononuclear cells (NBM MNC) per plate with methylcellulose medium containing cytokines SCF and EPO. Mean Colony forming units-granulocytes, erythrocytes, macrophages, megakaryocytes (CFU-GEMM) were assessed with and without the addition of FLCM. It was found that FLCM enhanced the number of colonies made by NBM MNCs. Further, cytokines IL-6 and Flt-3, present in FLCM, were bioneutralized with respective anti-cytokine antibodies. Neutralized FLCM was evaluated for the colony-forming potential of CFU-GEMM colonies. The maximum reduction of 42% was seen with 20 ng/ml of anti-IL-6 antibody. Maximum suppression up to 20% was observed with 0.7 ng/ml of anti Flt-3 antibody for CFU-GEMM colonies. Presence of cytokines IL-6 and Flt-3 in FL extracts and their colony stimulatory activity suggests that fetal liver infusion (FLI) may be a valuable alternative for managing BM recovery in certain clinical conditions such as AA.

Anti-CD117 antibody depletes normal and myelodysplastic syndrome human hematopoietic stem cells in xenografted mice.

The myelodysplastic syndromes (MDS) represent a group of clonal disorders that result in ineffective hematopoiesis and are associated with an increased risk of transformation into acute leukemia. MDS arises from hematopoietic stem cells (HSCs); therefore, successful elimination of MDS HSCs is an important part of any curative therapy. However, current treatment options, including allogeneic hematopoietic cell transplantation (HCT), often fail to ablate disease-initiating MDS HSCs, and thus have low curative potential and high relapse rates. Here, we demonstrate that human HSCs can be targeted and eliminated by monoclonal antibodies (mAbs) that bind cell-surface CD117 (c-Kit). We show that an anti-human CD117 mAb, SR-1, inhibits normal cord blood and bone marrow HSCs in vitro. Furthermore, SR-1 and clinical-grade humanized anti-human CD117 mAb, AMG 191, deplete normal and MDS HSCs in vivo in xenograft mouse models. Anti-CD117 mAbs also facilitate the engraftment of normal donor human HSCs in MDS xenograft mouse models, restoring normal human hematopoiesis and eradicating aggressive pathologic MDS cells. This study is the first to demonstrate that anti-human CD117 mAbs have potential as novel therapeutics to eradicate MDS HSCs and augment the curative effect of allogeneic HCT for this disease. Moreover, we establish the foundation for use of these antibody agents not only in the treatment of MDS but also for the multitude of other HSC-driven blood and immune disorders for which transplant can be disease-altering.

Ageratum conyzoides L. and Its Secondary Metabolites in the Management of Different Fungal Pathogens.

Ageratum conyzoides L. (Family-Asteraceae) is an annual aromatic invasive herb, mainly distributed over the tropical and subtropical regions of the world. It owns a reputed history of indigenous remedial uses, including as a wound dressing, an antimicrobial, and mouthwash as well as in treatment of dysentery, diarrhea, skin diseases, etc. In this review, the core idea is to present the antifungal potential of the selected medicinal plant and its secondary metabolites against different fungal pathogens. Additionally, toxicological studies (safety profile) conducted on the amazing plant A. conyzoides L. are discussed for the possible clinical development of this medicinal herb. Articles available from 2000 to 2020 were reviewed in detail to exhibit recent appraisals of the antifungal properties of A. conyzoides. Efforts were aimed at delivering evidences for the medicinal application of A. conyzoides by using globally recognized scientific search engines and databases so that an efficient approach for filling the lacunae in the research and development of antifungal drugs can be adopted. After analyzing the literature, it can be reported that the selected medicinal plant effectively suppressed the growth of numerous fungal species, such as Aspergillus, Alternaria, Candida, Fusarium, Phytophthora, and Pythium, owing to the presence of various secondary metabolites, particularly chromenes, terpenoids, flavonoids and coumarins. The possible mechanism of action of different secondary metabolites of the plant against fungal pathogens is also discussed briefly. However, it was found that only a few studies have been performed to demonstrate the plant's dosage and safety profile in humans. Considered all together, A. conyzoides extract and its constituents may act as a promising biosource for the development of effective antifungal formulations for clinical use. However, in order to establish safety and efficacy, additional scientific research is required to explore chronic toxicological effects of ageratum, to determine the probability of interactions when used with different herbs, and to identify safe dosage. The particulars presented here not only bridge this gap but also furnish future research strategies for the investigators in microbiology, ethno-pharmacology, and drug discovery.

Data driven estimation of novel COVID-19 transmission risks through hybrid soft-computing techniques.

Coronavirus genomic infection-2019 (COVID-19) has been announced as a serious health emergency arising international awareness due to its spread to 201 countries at present. In the month of April of the year 2020, it has certainly taken the pandemic outbreak of approximately 11,16,643 infections confirmed leading to around 59,170 deaths have been recorded world-over. This article studies multiple countries-based pandemic spread for the development of the COVID-19 originated in the China. This paper focuses on forecasting via real-time responses data to inherit an idea about the increase and maximum number of virus-infected cases for the various regions. In addition, it will help to understand the panic that surrounds this nCoV-19 for some intensely affecting states possessing different important demographic characteristics that would be affecting the disease characteristics. This study aims at developing soft-computing hybrid models for calculating the transmissibility of this genome viral. The analysis aids the study of the outbreak of this virus towards the other parts of the continent and the world. A hybrid of wavelet decomposed data into approximations and details then trained & tested through neuronal-fuzzification approach. Wavelet-based forecasting model predicts for shorter time span such as five to ten days advanced number of confirmed, death and recovered cases of China, India and USA. While data-based prediction through interpolation applied through moving average predicts for longer time spans such as 50-60 days ahead with lesser accuracy as compared to that of wavelet-based hybrids. Based on the simulations, the significance level (alpha) ranges from 0.10 to 0.67, MASE varying from 0.06 to 5.76, sMAPE ranges from 0.15 to 1.97, MAE varies from 22.59 to 6024.76, RMSE shows a variation from 3.18 to 8360.29 & R2 varying through 0.0018 to 0.7149. MASE and sMAPE are relatively lesser applied and novel measures that aimed to achieve increase in accuracy. They eliminated skewness and made the model outlier-free. Estimates of the awaited outburst for regions in this study are India, China and the USA that will help in the improvement of apportionment of healthcare facilities as it can act as an early-warning system for government policy-makers. Thus, data-driven analysis will provide deep insights into the study of transmission of this viral genome estimation towards immensely affected countries. Also, the study with the help of transmission concern aims to eradicate the panic and stigma that has spread like wildfire and has become a significant part of this pandemic in these times.

Salivary biomarkers in non-invasive oral cancer diagnostics: a comprehensive review.

OBJECTIVE: This review aims to provide a comprehensive analysis of the effectiveness of saliva as a non-invasive diagnostic marker for oral cancer. Despite progress in oral cancer diagnosis and prognosis, the 5-year survival rate remains low due to the resistance to treatment and delayed diagnosis, which can be attributed to various factors including tobacco and alcohol consumption, genetic damage, and human papillomavirus (HPV). The potential use of saliva as an easily accessible non-invasive screening and diagnostic method arises from its direct contact with the lesion site. METHODOLOGY: Data for this study were gathered via a comprehensive literature evaluation using search engines such as the PubMed, Web of Science, Google Scholar, and SciFinder. RESULTS: Identifying salivary biomarkers shows potential to transform oral cancer diagnostics by offering a reliable alternative to the traditional invasive methods. Saliva is an abundant reservoir for both cell-bound and cell-free organic and inorganic constituents. Thus, saliva is an appropriate field for research in proteomics, genomics, metagenomics, and metabolomics. CONCLUSION: This review provides a comprehensive elucidation of salivary biomarkers and their function in non-invasive oral cancer diagnosis, demonstrating their potential to enhance patient outcomes and reduce the impact of this devastating disease.

Salivary cysteine levels as a potential biochemical indicator of oral cancer risk in tobacco consumers.

Aim: Oral cancer is the leading cause of mortality, with a survival rate of less than 5 years, and is predominantly influenced by tobacco mutagens. Invasive diagnostic methods hinder early detection of oral cancer biomarkers. The present study performed salivary biochemical analysis for early oral cancer screening in tobacco consumers.Materials & methods: Three study groups included healthy controls (n = 25), tobacco users (n = 25) and oral cancer patients (n = 25). Salivary total protein, amylase, TNF-α and amino acid levels were evaluated using enzymatic tests, Enzyme linked Immunosorbent Assay (ELISA) and High-Performance Liquid Chromatography (HPLC).Results: Compared with healthy controls, salivary total protein and TNF-α levels were significantly (p = 0.04) higher in oral cancer patients. Salivary amylase levels were significantly lower in tobacco smokers (p = 0.02) and higher in oral cancer patients (p = 0.01). Interestingly, the amino acid cysteine concentration was significantly higher (p = 0.02) in tobacco consumers (62.5 ± 10) than in healthy controls (116.1 ± 28).Conclusion: In high-risk populations, such as tobacco users, salivary biochemical analysis can serve as a promising noninvasive diagnostic method for early oral cancer screening. As a salivary biomarker, the amino acid cysteine exhibits potential as a means of detecting the progression of oral cancer in individuals who consume tobacco.

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Enhancing Proliferation of Stem Cells from Human Exfoliated Deciduous Teeth (SHED) through hTERT Expression while Preserving Stemness and Multipotency.

BACKGROUND: Stem cells from human exfoliated deciduous teeth (SHED) hold promise in regenerative medicine owing to their multipotent capabilities resembling mesenchymal stem cells (MSCs). Despite their potential, SHED have not been extensively investigated because their limited lifespan and unavailability of cell-lines pose challenges for therapeutic applications. This study investigated the effect of ectopic human telomerase reverse transcriptase (hTERT) expression on SHEDs' proliferation while preserving stemness and genomic integrity. METHODS: Deciduous teeth were collected from children aged 6-10 years. After isolation and characterization, the SHED were transduced with pBabe-puro-hTERT retrovirus to establish SHED cell-line, which was evaluated and compared with pBabe-puro (mock control) for stemness, multipotency and growth attributes through flow cytometry, trilineage differentiation, and growth kinetics. We also estimated hTERT gene expression, genomic integrity, and validated cell-line through STR analysis. RESULTS: Following hTERT transduction, SHED displayed elevated hTERT gene expression while retaining fibroblast-like morphology and mesenchymal stem cell markers. Moreover, after hTERT transduction cellular shape remained same along with increased replicative lifespan and proliferation potential. SHED-hTERT cells exhibited multi-potency and maintained stemness, as evidenced by surface marker expression and multilineage differentiation. Furthermore, genomic integrity was not affected by hTERT integration, as confirmed by STR analysis and CDKN2A gene assessment. CONCLUSION: Ectopic hTERT expression in SHED successfully prolonged their replicative lifespan and improved their ability to proliferate and migrate, while preserving their stemness, multipotency and genomic integrity, suggesting minimal carcinogenic risk. Establishment of SHED cell-line holds potential in regenerative medicine applications, especially in cell-based drugs and tissue engineering experiments.

Extraction and characterization of exosomes from the exhaled breath condensate and sputum of lung cancer patients and vulnerable tobacco consumers-potential noninvasive diagnostic biomarker source.

Noninvasive sample sources of exosomes, such as exhaled breath and sputum, which are in close proximity to the tumor microenvironment and may contain biomarkers indicative of lung cancer, are far more permissive than invasive sample sources for biomarker screening. Standardized exosome extraction and characterization approaches for low-volume noninvasive samples are critically needed. We isolated and characterized exhaled breath condensate (EBC) and sputum exosomes from healthy nonsmokers (n= 30), tobacco smokers (n= 30), and lung cancer patients (n= 40) and correlated the findings with invasive sample sources. EBC samples were collected by using commercially available R-Tubes. To collect sputum samples the participants were directed to take deep breaths, hold their breath, and cough in a collection container. Dynamic light scattering, nanoparticle tracking analysis, and transmission electron microscopy were used to evaluate the exosome morphology. Protein isolation, western blotting, exosome quantification via EXOCET, and Fourier transform infrared spectroscopy were performed for molecular characterization. Exosomes were successfully isolated from EBC and sputum samples, and their yields were adequate and sufficiently pure for subsequent downstream processing and characterization. The exosomes were confirmed based on their size, shape, and surface marker expression. Remarkably, cancer exosomes were the largest in size not only in the plasma subgroups, but also in the EBC (p < 0.05) and sputum (p= 0.0036) subgroups, according to our findings. A significant difference in exosome concentrations were observed between the control sub-groups (p < 0.05). Our research confirmed that exosomes can be extracted from noninvasive sources, such as EBC and sputum, to investigate lung cancer diagnostic biomarkers for research, clinical, and early detection in smokers.

Reduced ribosomal protein gene dosage and p53 activation in low-risk myelodysplastic syndrome.

Reduced gene dosage of ribosomal protein subunits has been implicated in 5q- myelodysplastic syndrome and Diamond Blackfan anemia, but the cellular and pathophysiologic defects associated with these conditions are enigmatic. Using conditional inactivation of the ribosomal protein S6 gene in laboratory mice, we found that reduced ribosomal protein gene dosage recapitulates cardinal features of the 5q- syndrome, including macrocytic anemia, erythroid hypoplasia, and megakaryocytic dysplasia with thrombocytosis, and that p53 plays a critical role in manifestation of these phenotypes. The blood cell abnormalities are accompanied by a reduction in the number of HSCs, a specific defect in late erythrocyte development, and suggest a disease-specific ontogenetic pathway for megakaryocyte development. Further studies of highly purified HSCs from healthy patients and from those with myelodysplastic syndrome link reduced expression of ribosomal protein genes to decreased RBC maturation and suggest an underlying and common pathophysiologic pathway for additional subtypes of myelodysplastic syndrome.

Ameliorative potential of stem cells from human exfoliated deciduous teeth (SHED) in preclinical studies: A meta-analysis.

The preclinical and clinical role of mesenchymal stem cells from various adult sources is extensively investigated and established in regenerative medicine. However, the comprehensive exploration of the therapeutic potential of Stem cells from human exfoliated deciduous teeth (SHED) is inadequate. Therefore, we performed a systematic meta-analysis of preclinical animal model studies in several diseases to provide insight into SHED's efficacy and therapeutic potential. Two blinded and independent investigators searched the available online databases and scrutinized the included studies. Meta-analysis was performed to evaluate the pooled effect estimate of intervention of SHED by Review Manager 5.4.1. To investigate the therapeutic efficacy of SHED intervention, we also analyzed the test of heterogeneity (I2), overall effect (Z), sensitivity, and publication bias. Among the 2156 scrutinized studies, 40 were included and evaluated as per inclusion and exclusion criteria. The intervention of SHED and its derivatives in several diseases depicted statistically significant therapeutic effects in periodontitis, pulpitis, spinal cord injury, parkinson's disease, alzheimer's disease, focal cerebral ischemia, peripheral nerve injury, and retinal pigmentosa. SHED also improved levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin in liver fibrosis . In autoimmune diseases also, values were significant. SHED also showed a statistically significant reduction of wound healing area and new bone formation in bone defects. The pooled effect estimates of included preclinical studies demonstrated a statistically significant therapeutic effect of SHED in numerous diseases. Based on our data, it is suggested that the potential of SHED may be implemented in clinical trials after conducting a few more preclinical studies.

Exploring salivary exosomes as early predictors of oral cancer in susceptible tobacco consumers: noninvasive diagnostic and prognostic applications.

BACKGROUND: Salivary exosome analysis provides a noninvasive and comprehensive approach with potential applications in oral cancer diagnosis and prognosis. The early detection of oral cancer has remained a critical concern in enhancing the quality of life, especially for individuals who consume tobacco and are at greater risk of developing the disease. The current study investigates the potential of salivary exosomes in screening smokers for early signs and transformations of oral cancer. METHODS: Morphological characterization of salivary exosomes among three study groups (non-smokers as control, smokers as high-risk tobacco consumers, and Oral cancer) (n = 120) was carried out through dynamic light scattering, and nanoparticle tracking analysis. For molecular characterization, EXOCET and Fourier transform infrared spectroscopy methods were utilized. The expression of the exosomal surface protein CD63 was evaluated using Western blotting. RESULTS: Salivary exosomes exhibit noticeable differences in size between control group and tobacco consumers. The differentiation extended beyond exosome size and included variations in concentration and bio-molecular composition, as determined by FTIR screening. Tobacco consumers and oral cancer groups showed significantly larger and more concentrated exosomes compared to the healthy group. CONCLUSION: Our study provides strong evidence that the properties of salivary exosomes can serve as reliable noninvasive biomarkers for distinguishing tobacco consumers from non-smokers and oral cancer patients. Our results underscore the potential of exosome-based diagnostics in early oral cancer detection for high-risk individuals. The larger size and higher concentration of exosomes in tobacco consumers indicate early changes in cell secretions associated with the transformation from healthy to abnormal cells.

Cyclodextrin-Based Arsenal for Anti-Cancer Treatments.

Anti-cancer drugs are mostly limited in their use due to poor physicochemical and biopharmaceutical properties. Their lower solubility is the most common hurdle limiting their use upto their potential. In the recent years, the cyclodextrin (CD) complexation have emerged as existing approach to overcome the problem of poor solubility. CD-based nano-technological approaches are safe, stable and showed well in vivo tolerance and greater payload for encapsulation of hydrophobic drugs for the targeted delivery. They are generally chosen due to their ability to get self-assembled to form liposomes, nanoparticles, micelles and nano-sponges etc. This review paper describes a birds-eye view of the various CD-based nano-technological approaches applied for the delivery of anti-cancer moieties to the desired target such as CD based liposomes, niosomes, niosoponges, micelles, nanoparticles, monoclonal antibody, magnetic nanoparticles, small interfering RNA, nanorods, miscellaneous formulation of anti-cancer drugs containing CD. Moreover, the author also summarizes the various shortcomings of such a system and their way ahead.

Patients' perspectives on timing of urinary catheter removal after surgery.

UNLABELLED: A prolonged catheter duration is a major risk factor for catheter-associated urinary tract infection, with bacteriuria increasing by 5% per day (Gokula et al, 2004). AIM: In this study, the authors explored patients' perceptions of the care process relating to peri-operative catheterisation to identify patient factors that encourage early removal. METHOD: Semi-structured interviews, incorporating a grounded theory approach, were performed on three men and seven women during 2010. Interviews were transcribed and analysed using constant comparative method and thematic framework analysis. RESULTS: Catheter duration ranged 1-10 days. Main themes elicited included: lack of understanding of the purpose and catheterisation process; loss of patient autonomy and dignity; and impact of environmental factors. CONCLUSION: Lack of knowledge of the catheterisation process among participants led to fears and concerns that may have contributed to delayed catheter removal. Changes to patient care that are likely to reduce catheter duration include ensuring the provision of pre-operative information, greater patient involvement in catheter removal decisions, and provision of easily accessible toilet facilities.

Hybridized wavelet neuronal learning-based modelling to predict novel COVID-19 effects in India and USA.

Coronavirus disease so called as COVID-19 is an infectious disease and its spread takes place due to human interaction by their pathogen materials during coughing and sneezing. COVID-19 is basically a respiratory disease as evidence proved that a large number of infected people died due to short breathing. Most widely and uncontrollably spreading unknown viral genome infecting people worldwide was announced to be 2019-2020 nCoV by WHO on January 30, 2020. Based on the seriousness of its spread and unavailability of vaccination or any form of treatment, it was an immediate health-emergency of concern of international-level. The paper analyses effects of this virus in countries, such as India and United States on day-to-day basis because of their greater variability. In this study, various performance measures, such as root mean square error (RMSE), mean absolute error (MAE), coefficient of determination ( R 2 ) , mean absolute standard error (MASE) and mean absolute percentage error (MAPE) which characterize models' performances. R 2 value has been achieved to be closest to 1, i.e., 0.999 from Wavelet Neuronal Network Fuzzified Inferences' Layered Multivariate Adaptive Regression Spline (WNNFIL-MARS) for both the countries' data. It is important to capture the essence of this pandemic affecting millions of the population daily ever since its spread began from January, 2020.

Exosomics in oral cancer diagnosis, prognosis, and therapeutics - An emergent and imperative non-invasive natural nanoparticle-based approach.

Exosomes- the natural nanoparticles belonging to heterogeneous vesicles are released via nearly all sorts of cells, including tumour cells, to oprate intercellular communication. Selective packaging of exosomes amid nucleic acids, phospholipids, and proteins makes them ideal for intercellular communications occurring among different cells. The existence of exosomes has been validated in various biofluids, including saliva. Being non-invasive and in direct contact with oral malignant cells, saliva establishes itself as a preeminent source of early cancer biomarkers. In context, the role and providence of both recipient and donor secreting cells are persuaded through exosomal cargo.Several studies have emphasized the influence of exosomal contents in different stages of cancer development, reconciling interactions between tumour cells and their surrounding niche. More explicitly, a transformation of exosomal contents such as nucleic acids, lipids, and proteins can endorse tumour progression and help ascertain a secluded pre-metastatic niche crammed with substances that errand cancer cell proliferation,angiogenesis, metastasis, and drug resistance. The blooming field of exosomes has directed the evolution of high-end isolation and characterization techniques along with the development of an entirely new field- exosomics that comprises complete analysis of exosomal cargo in various physiological conditions, including oral cancer. Researchers have discovered multiple pathways involved in exosome biogenesis to understand numerous events associated with cancer progression. Tissue-specific packaging of exosomes makes them a novel source of prognostic and diagnostic biomarkers and potential therapeutic targets. The extent of the current review confers the contemporary perception of the versatile task of exosomes, especially salivary exosomes, as potential biomarkers in the progression and diagnosis as well as therapeutics of oral cancers and their potential employment in clinical applications.

Cytotoxic Role of Chlorogenic Acid on Oral Squamous Cell Carcinoma Cell Line.

The aim of the present study was to determine the cytotoxic, anticancerous and antiproliferative activity of CGA on oral squamous cell carcinoma (OSCC) cell line (KB) and to evaluate expression level of p21 and p53 in these CGA treated OSCC cell line. Different concentrations of CGA varying from 500 to 2500 µM were tested on OSCC cell line. Trypan blue and MTT assay were performed to establish IC50. DNA fragmentation and expression level of p21 and p53 were evaluated with the help of RT-PCR. CGA exerted antiproliferative and cytotoxic effect on OSCC (KB) cell line. Statistically significant results were found regarding effect of different CGA concentrations on KB cell line with IC50 at 1800 µM. No DNA fragmentation was observed. p21 and p53 expression were down regulated after CGA treatment. CGA revealed neither apoptosis nor damage to the nucleus after DNA fragmentation. Antiproliferative role of CGA was hinted by down regulation of p53 and p21 probably through cell cycle arrest at G1-S phase. It was reaffirmed that CGA a natural chemo preventive agent could enhance the treatment modalities with minimal side effects.

A Phytochemicals Approach Towards the Treatment of Cervical Cancer Using Polyphenols and Flavonoids.

AIM: Despite enormous progress in cancer biology, oncologists are still struggling to retrieve the methods and drugs to cure cancer which remains a global threat to humans. Plant-derived natural compounds, also known as phytochemicals, carry therapeutic potential and could be taken as dietary supplements, which are a radical way to resist as well as cure cancer. The present study reveals the anti-cancerous potential of a few phytochemical constituents under in vitro conditions and their mode of action on cervical cancer. SiHa was treated with phytochemicals viz. Quercetin dihydrate, Gallic Acid, and Naringin with varying concentrations to assess their cytotoxicity potential by various methods and also to elucidate their IC50 values. METHODS: All three compounds reduced the cell number and viability, along with alterations in cancer cell morphology. The diagnosed IC50 values of the compounds were 160µM, 200µM, and 1500µM for Quercetin dihydrate, Gallic Acid, and Naringin, respectively. DNA fragmentation assay and gene expression analysis were also used to assess apoptosis and anti-proliferative activity of compounds. RESULTS: We found fragmented DNA in treated cells as assessed by gel electrophoresis assay. These phytochemicals elicit an apoptotic response in SiHa cells by significantly up-regulating the gene expression level of p53 and p21 (p-value <0.005). CONCLUSION: Considering the anti-cancer and anti-proliferative potential of Quercetin dihydrate, Gallic Acid, and Naringin on the cervical cancer cell line, these phytochemicals could be used as an alternative or concurrent cancer therapeutic approach. However, further in-depth elucidation of their mode of action, safety, and efficacy should be explored.

Machine learned hybrid Gaussian analysis of COVID-19 pandemic in India.

This article discusses short term forecasting of the Novel Corona Virus (COVID -19) data for infected, recovered and active cases using the Machine learned hybrid Gaussian and ARIMA method for the spread in India. The Covid-19 data is obtained from the World meter and MOH (Ministry of Health, India). The data is analyzed for the period from January 30, 2020 (the first case reported) to October 15, 2020. Using ARIMA (2, 1, 0), we obtain the short forecast up to October 31, 2020. The several statistics parameters have tested for the goodness of fit to evaluate the forecasting methods but the results show that ARIMA (2, 1, 0) gives better forecast for the data system. It is observed that COVID 19 data follows quadratic behavior and in long run it spreads with high peak roughly estimated in September 18, 2020. Also, using nonlinear regression it is observed that the trend in long run follows the Gaussian mixture model. It is concluded that COVID 19 will follow secondary shock wave in the month of November 2020. In India we are approaching towards herd immunity. Also, it is observed that the impact of pandemic will be about 441 to 465 days and the pandemic will end in between April-May 2021. It is concluded that primary peak observed in September 2020 and the secondary shock wave to be around November 2020 with sharp peak. Thus, it is concluded that the people should follow precautionary measures and it is better to maintain social distancing with all safety measures as the pandemic situation is not in control due to non-availability of medicines.

Nonlinear dynamics for the spread of pathogenesis of COVID-19 pandemic.

Coronaviruses did not invite attention at a global level and responsiveness until the series of 2003-SARS contagion followed by year-2012 MERS plus, most recently, 2019-nCoV eruptions. SARS-CoV &MERS-CoV are painstaking, extremely pathogenic. Also, very evidently, both have been communicated from bats to palm-civets & dromedary camels and further transferred ultimately to humans. No country has been deprived of this viral genomic contamination wherever populaces reside and are interconnected. This study aimed to develop a mathematical model for calculating the transmissibility of this viral genome. The analysis aids the study of the outbreak of this Virus towards the other parts of the continent and the world. The parameters such as population mobility, natural history, epidemiological characteristics, and the transmission mechanism towards viral spread when considered into crowd dynamism result in improved estimation. This article studies the impact of time on the amount of susceptible, exposed, the infected person taking into account asymptomatic and symptomatic ones; recovered i.e., removed from this model and the virus particles existing in the open surfaces. The transition from stable phase to attractor phase happens after 13 days i.e.; it takes nearly a fortnight for the spread to randomize among people. Further, the pandemic transmission remains in the attractor phase for a very long time if no control measures are taken up. The attractor-source phase continues up to 385 days i.e., more than a year, and perhaps stabilizes on 386th day as per the Lyapunov exponent's analysis. The time series helps to know the period of the Virus's survival in the open sources i.e. markets, open spaces and various other carriers of the Virus if not quarantined or sanitized. The Virus cease to exist in around 60 days if it does not find any carrier or infect more places, people etc. The changes in LCEs of all variables as time progresses for around 400 days have been forecasted. It can be observed that phase trajectories indicate how the two variables interact with each other and affect the overall system's dynamics. It has been observed that for exposed and asymptomatically infected (y-z), as exposed ones (y) change from 0 to 100 the value of asymptomatically infected (z) increased upto around 58, at exposed ones (y)=100, asymptomatically infected (z) has two values as 58 and 10 i.e. follows bifurcation and as exposed ones (y) changes values upto 180, the value of asymptomatically infected (z) decreases to 25 so for exposed ones (y) from 100 to 180, asymptomatically infected (z) varies from 58 to 25 to 10 follows bifurcation. Also, phase structures of exposed-symptomatically infected (y-u), exposed-removed (y-v), exposed-virus in the reservoir (y-w), asymptomatically infected-removed (z-v), symptomatically infected-removed (u-v) specifically depict bifurcations in various forms at different points. In case of asymptomatically infected-virus in the reservoir (z-w), at asymptomatically infected (z)=10, the value of viruses in the reservoir (w)=50, then as asymptomatically infected (z) increases to upto around 60. At this point, removed ones (v) increase from 50 to 70 and asymptomatically infected (z) decrease to 20 i.e., crosses the same value twice, which shows its limiting is known as limit cycle behavior and both the values tend to decrease towards zero. It shows a closed-loop limit cycle. Today, there has been no scientific revolution in the development of vaccination, nor has any antiviral treatment been successful, resulting in lack of its medication. Based on the phases, time series, and complexity analysis of the model's various parameters, it is studied to understand the variation in this pandemic's scenario.