The implication of microbiome in lungs cancer: mechanisms and strategies of cancer growth, diagnosis and therapy.

Available evidence illustrates that microbiome is a promising target for the study of growth, diagnosis and therapy of various types of cancer. Lung cancer is a leading cause of cancer death worldwide. The relationship of microbiota and their products with diverse pathologic conditions has been getting large attention. The novel research suggests that the microbiome plays an important role in the growth and progression of lung cancer. The lung microbiome plays a crucial role in maintaining mucosal immunity and synchronizing the stability between tolerance and inflammation. Alteration in microbiome is identified as a critical player in the progression of lung cancer and negatively impacts the patient. Studies suggest that healthy microbiome is essential for effective therapy. Various clinical trials and research are focusing on enhancing the treatment efficacy by altering the microbiome. The regulation of microbiota will provide innovative and promising treatment strategies for the maintenance of host homeostasis and the prevention of lung cancer in lung cancer patients. In the current review article, we presented the latest progress about the involvement of microbiome in the growth and diagnosis of lung cancer. Furthermore, we also assessed the therapeutic status of the microbiome for the management and treatment of lung cancer.

Implication of calcium supplementations in health and diseases with special focus on colorectal cancer.

Calcium is a fundamental and integrative element and helps to ensure optimal health by regulating various physiological and pathological processes. While there is substantiated evidence confirming the beneficial effects of calcium in the treatment, management, and prevention of various health conditions, including cancer, conflicting studies are imperative to acknowledge the potential negative role of calcium supplementation. The studies on calcium supplementation showed that a specific dose can help in the maintenance of good human health, and in the control of different types of diseases, including cancer. Calcium alone and when combined with vitamin D, emerges as a promising therapeutic option for efficiently managing cancer growth, when used with chemotherapy. Combination therapy is considered a more effective approach for treating advanced types of colorectal cancer. Nevertheless, several challenges drastically influence the treatment of cancer, such as individual discrepancy, drug resistance, and stage of cancer, among others. Henceforth, novel preventive, reliable therapeutic modalities are essential to control and reduce the incidence and mortality of colorectal cancer (CRC). The calcium-sensing receptor (CaSR) plays a pivotal role in calcium homeostasis, metabolism, and regulation of oncogenesis. Numerous studies have underscored the potential of CaSR, a G protein-coupled receptor, as a potential biomarker and target for colorectal cancer prevention and treatment. The multifaceted involvement of CaSR in anti-inflammatory and anti-carcinogenic processes paves the way for its utilization in the diagnosis and management of colorectal cancer. The current review highlights the important role of supplemental calcium in overall health and disease, along with the exploration of intricate mechanisms of CaSR pathways in the management and prevention of colorectal cancer.

Analysis of prevalence of adverse events connected with anti-tuberculosis drugs during pregnancy: A meta-analysis.

Background: Mycobacterium tuberculosis infection is transmitted among humans via airborne droplets. The drugs used in the initial treatment regimen for tuberculosis (TB) cross the placenta, raising some concerns regarding their safety during pregnancy may provide a more valid approach for evaluating the relative influence of various risk factors. Adverse events of anti-tuberculous (anti-TB) drug during pregnancy remain uncertain and controversial issues. Methods: We performed a systematic analysis to study the adverse events connected with anti-TB drugs usage during pregnancy. The risk of bias in the included studies was assessed using the Cochrane Collaboration criteria. Interstudy heterogeneity was assessed via Cochran's test. Assuming heterogeneity, a random-effects model was applied. Outcomes were pooled using the inverse variance method. Besides, a funnel plot was created to assess publication bias. We used Egger's linear regression test of funnel plot asymmetry, modified to accommodate inter-study heterogeneity. Effect estimates and confidence intervals for all studies were depicted on a forest plot. Results: The prevalence of total adverse events for all anti-TB drugs was 25.9 %. According to the drug category, the prevalence of total adverse events was 50 % for ethambutol, 32.6 % for the six-month directly observed treatment short-course (DOTS), 31.4 % for the nine-month DOTS, and 13.7 % for isoniazid. Conclusions: There is a high rate of reported adverse events associated with anti-TB drugs usage during pregnancy. We concluded that more high-quality clinical studies and research works are needed to reach a conclusive decision on the safety of the treatment of TB among pregnant women.

Curcumin's Dose-Dependent Attenuation of Gastric Cancer Cell Progression Via the PI3K Pathway Blockade.

Background: Gastric cancer stands as a primary cause of cancer-related deaths worldwide, making the discovery of new therapeutic agents essential for enhancing treatment outcomes. Curcumin, a polyphenolic compound found in turmeric (Curcuma longa), has demonstrated potential in multiple cancer types due to its anti-cancer characteristics. This research aimed to examine the impact of curcumin on gastric cancer cell growth, migration, and invasion, as well as its influence on the phosphoinositide 3-kinase (PI3K) signaling cascade. Methods: Gastric cancer cell lines were exposed to varying curcumin concentrations, followed by assessments of cell viability, migration, and invasion. Furthermore, gene and protein expression levels associated with the PI3K signaling cascade were evaluated using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Results: The findings revealed a dose-dependent decrease in cell viability, migration, and invasion in gastric cancer cells treated with curcumin. Additionally, curcumin administration led to the downregulation of key genes and proteins within the PI3K signaling process, such as PI3K, Akt, and mTOR. Conclusion: These findings propose that curcumin may exercise its anti-cancer effects on gastric cancer cells, partly by suppressing the PI3K signaling pathway. This study's outcomes support curcumin's potential as a therapeutic agent for gastric cancer and encourage further exploration of its underlying molecular mechanisms and in vivo effectiveness.

Association of mTOR Pathway and Conformational Alterations in C-Reactive Protein in Neurodegenerative Diseases and Infections.

Inflammatory biomarkers have been very useful in detecting and monitoring inflammatory processes along with providing helpful information to select appropriate therapeutic strategies. C-reactive protein (CRP) is a nonspecific, but quite useful medical acute inflammatory biomarker and is associated with persistent chronic inflammatory processes. Several studies suggest that different levels of CRP are correlated with neurological disorders such as Alzheimer's disease (AD). However, dynamics of CRP levels have also been observed in virus/bacterial-related infections leading to inflammatory responses and this triggers mTOR-mediated pathways for neurodegeneration diseases. The biophysical structural transition from CRP to monomeric CRP (mCRP) and the significance of the ratio of CRP levels on the onset of symptoms associated with inflammatory response have been discussed. In addition, mTOR inhibitors act as immunomodulators by downregulating the expression of viral infection and can be explored as a potential therapy for neurological diseases.

Drug Standardization through Pharmacognostic Approaches and Estimation of Anticancer Potential of Chamomile (Matricaria chamomilla L.) using Prostate-Cancer cell lines: An In-vitro Study.

Cancer is the major challenge across world and the adenocarcinoma of prostate malignancy is the second most prevalent male cancer. Various medicinal plants are used for the treatment and management of various cancers. Matricaria chamomilla L., is one of the extensively used Unani medicament for the treatment of various type of diseases. In the current study we evaluated most of the parameters prescribed for drug standardization using pharmacognostic approaches. The 2,2 Diphenyl-1-picryl hydrazyl (DPPH) method was utilized for the analysis of antioxidant activity in the flower extracts of M. chamomilla. Moreover, we analyzed the antioxidant and cytotoxic activity of M. chamomilla (Gul-e Babuna) through in-vitro method. DPPH (2,2-diphenyl-1-picryl-hydrazl-hydrate) method was utilized for the analysis of antioxidant activity in the flower extracts of M. chamomilla. CFU and wound healing assay were performed to determine the anti-cancer activity. The results demonstrated that various extracts of M. chamomilla fulfilled most of the parameters of drug standardization and contained good antioxidant and anticancer activities. The ethyl acetate showed higher anticancer activity followed by aqueous, hydroalcoholic, petroleum benzene and methanol by CFU method. Also, the wound healing assay demonstrated that ethyl acetate extract has more significant effect followed by methanol and petroleum benzene extract on prostate cancer cell line (C4-2). The current study concluded that the extract of M. chamomilla flowers could act as good source of natural anti-cancer compounds.

Implications of trimethylamine N-oxide (TMAO) and Betaine in Human Health: Beyond Being Osmoprotective Compounds.

Osmolytes are naturally occurring small molecular weight organic molecules, which are accumulated in large amounts in all life forms to maintain the stability of cellular proteins and hence preserve their functions during adverse environmental conditions. Trimethylamine N-oxide (TMAO) and N,N,N-trimethylglycine (betaine) are methylamine osmolytes that have been extensively studied for their diverse roles in humans and have demonstrated opposing relations with human health. These osmolytes are obtained from food and synthesized endogenously using dietary constituents like choline and carnitine. Especially, gut microbiota plays a vital role in TMAO synthesis and contributes significantly to plasma TMAO levels. The elevated plasma TMAO has been reported to be correlated with the pathogenesis of numerous human diseases, including cardiovascular disease, heart failure, kidney diseases, metabolic syndrome, etc.; Hence, TMAO has been recognized as a novel biomarker for the detection/prediction of several human diseases. In contrast, betaine acts as a methyl donor in one-carbon metabolism, maintains cellular S-adenosylmethionine levels, and protects the cells from the harmful effects of increased plasma homocysteine. Betaine also demonstrates antioxidant and anti-inflammatory activities and has a promising therapeutic value in several human diseases, including homocystinuria and fatty liver disease. The present review examines the multifarious functions of TMAO and betaine with possible molecular mechanisms towards a better understanding of their emerging and diverging functions with probable implications in the prevention, diagnosis, and treatment of human diseases.

Analysis of Anti-Arrhythmic Impacts of Crocin through Estimation of Expression of Cx43 in Myocardial Infarction Using a Rat Animal Model.

Arrhythmia is an important cause of death after myocardial infarction (MI). Different substances have been evaluated for their anti-arrhythmic effect in MI. This study was performed to evaluate the anti-arrhythmic impacts of crocin in an MI animal model (rat) by estimation of the expression of connexin 43 (Cx43). Fifty male Sprague-Dawley rats were grouped into 5 groups, each composed of 10 rats. The first group was regarded as the normal control group and the second one was considered as the MI group, which was caused by ligation of the left anterior descending artery. The other three groups received crocin 50 or 10 mg/kg/day or metoprolol 100 mg/kg/day for 1 week, following ligation of the left anterior descending artery. Evaluated outcomes were cardiac Cx43 expression, arrhythmia incidence, histological findings, and myocyte resting potential. Crocin-treated MI groups showed a significantly lower arrhythmia score than the non-treated MI group, 10 mg/kg/day (1.85 ± 0.55, p < 0.01) and 50 mg/kg/day (1.70 ± 0.33, p < 0.01). Groups that received crocin 10 mg/kg/day (66.30 ± 2.59, p < 0.01), crocin 50 mg/kg/day (68.10 ± 2.43, p < 0.01), and metoprolol 100 mg/kg/day (-63.54 ± 0.63 mV, p < 0.01) significantly prevented depolarization in comparison with the non-treated MI group. Expression of Cx43 mRNA in crocin 10 mg/kg/day (1.54 ± 0.24, p < 0.01), crocin 50 mg/kg/day (1.73 ± 0.09, p < 0.01), and metoprolol 100 mg/kg/day (1.75 ± 0.14, p < 0.01) treatment groups was significantly higher in comparison with the non-treated MI group. Crocin showed a preventive effect on the arrhythmogenic impact of MI in an experimental model of ischemic injury through an increase in expression of Cx43.

Withania somnifera (L.) Dunal (Ashwagandha) for the possible therapeutics and clinical management of SARS-CoV-2 infection: Plant-based drug discovery and targeted therapy.

Coronavirus disease 2019 (COVID-19) pandemic has killed huge populations throughout the world and acts as a high-risk factor for elderly and young immune-suppressed patients. There is a critical need to build up secure, reliable, and efficient drugs against to the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Bioactive compounds of Ashwagandha [Withania somnifera (L.) Dunal] may implicate as herbal medicine for the management and treatment of patients infected by SARS-CoV-2 infection. The aim of the current work is to update the knowledge of SARS-CoV-2 infection and information about the implication of various compounds of medicinal plant Withania somnifera with minimum side effects on the patients' organs. The herbal medicine Withania somnifera has an excellent antiviral activity that could be implicated in the management and treatment of flu and flu-like diseases connected with SARS-CoV-2. The analysis was performed by systematically re-evaluating the published articles related to the infection of SARS-CoV-2 and the herbal medicine Withania somnifera. In the current review, we have provided the important information and data of various bioactive compounds of Withania somnifera such as Withanoside V, Withanone, Somniferine, and some other compounds, which can possibly help in the management and treatment of SARS-CoV-2 infection. Withania somnifera has proved its potential for maintaining immune homeostasis of the body, inflammation regulation, pro-inflammatory cytokines suppression, protection of multiple organs, anti-viral, anti-stress, and anti-hypertensive properties. Withanoside V has the potential to inhibit the main proteases (Mpro) of SARS-CoV-2. At present, synthetic adjuvant vaccines are used against COVID-19. Available information showed the antiviral activity in Withanoside V of Withania somnifera, which may explore as herbal medicine against to SARS-CoV-2 infection after standardization of parameters of drug development and formulation in near future.

Optimization of Elicitation Conditions to Enhance the Production of Potent Metabolite Withanolide from Withania somnifera (L.).

This study aimed at optimizing conditions for increased withanolide production in Withania somnifera. The elicitors used for the foliar spray on the aerial parts of the plant were salicylic acid, jasmonic acid, and chitosan for the enhancement of withanolides in Withania somnifera under different environmental regimes. Three different elicitors, i.e., chitosan, jasmonic acid and salicylic acid, were applied on the plants through foliar route every 15th day for 6 months, and later plants were used for sample preparation. Further, the elicitors were used in different concentration, i.e., jasmonic acid (50, 200 and 400 ppm), chitosan (10, 50 and 100 ppm) and salicylic acid (0.5, 1 and 2 ppm). The elicitors were sprayed on the foliar parts of the plant between 10:00-11:00 a.m. on application days. For elicitor spray, a calibrated sprayer was used. The withanolide A/withaferin A was quantified through HPLC. It was found that in an open environment, maximum withaferin A content, i.e., 0.570 mg/g (DW), was recorded with jasmonic acid (50 ppm) treatment in comparison to control (0.067 mg/g DW). Thus, there was an 8.5-fold increase in the withaferin A content. Maximum withanolide A content of 0.352 mg/g (DW) was recorded when chitosan (50 ppm) was sprayed, while in the control, withanolide A content was recorded to be 0.031 mg/g (DW); thus, chitosan application increased the production of withanolide A by 11.3-fold. Under controlled conditions, maximum withaferin A content of 1.659 mg/g (DW) was recorded when plants were sprayed with chitosan (100 ppm), which was 8.1 times greater than the control content of 0.203 mg/g (DW). Maximum withanolide A content of 0.460 mg/g (DW) was recorded when chitosan (100 ppm) was applied, whereas in the control, withanolide A content was found to be 0.061 mg/g (DW). Thus, foliar spraying of elicitors in very low concentrations can serve as a low-cost, eco-friendly, labor-intensive and elegant alternative approach that can be practiced by farmers for the enhancement, consistent production and improved yield of withanolide A/withaferin A. This can be a suitable way to enhance plant productivity, thus increasing the availability of withanolide A and withaferin A for the health and pharma industry.

Deciphering the enigmatic crosstalk between prostate cancer and Alzheimer's disease: A current update on molecular mechanisms and combination therapy.

Alzheimer's disease (AD) and prostate cancer (PCa) are considered the leading causes of death in elderly people worldwide. Although both these diseases have striking differences in their pathologies, a few underlying mechanisms are similar when cell survival is considered. In the current study, we employed an in-silico approach to decipher the possible role of bacterial proteins in the initiation and progression of AD and PCa. We further analyzed the molecular connections between these two life-threatening diseases. The androgen deprivation therapy used against PCa has been shown to promote castrate resistant PCa as well as AD. In addition, cell signaling pathways, such as Akt, IGF, and Wnt contribute to the progression of both AD and PCa. Besides, various proteins and genes are also common in disease progression. One such similarity is mTOR signaling. mTOR is the common downstream target for many signaling pathways and plays a vital role in both PCa and AD. Targeting mTOR can be a favorable line of treatment for both AD and PCa. However, drug resistance is one of the challenges in effective drug therapy. A few drugs that target mTOR have now become ineffective due to the development of resistance. In that regard, phytochemicals can be a rich source of novel drug candidates as they can act via multiple mechanisms. This review also presents mTOR targeting phytochemicals with promising anti-PCa, anti-AD activities, and approaches to overcome the issues associated with phytochemical-based therapies in clinical trials.

Does COVID-19 lockdowns have impacted on global dengue burden? A special focus to India.

BACKGROUND: The world has been battling several vector-borne diseases since time immemorial. Socio-economic marginality, precipitation variations and human behavioral attributes play a major role in the proliferation of these diseases. Lockdown and social distancing have affected social behavioral aspects of human life and somehow impact on the spread of vector borne diseases. This article sheds light into the relationship between COVID-19 lockdown and global dengue burden with special focus on India. It also focuses on the interconnection of the COVID-19 pandemic (waves 1 and 2) and the alteration of human behavioral patterns in dengue cases. METHODS: We performed a systematic search using various resources from different platforms and websites, such as Medline; Pubmed; PAHO; WHO; CDC; ECDC; Epidemiology Unit Ministry of Health (Sri Lanka Government); NASA; NVBDCP from 2015 until 2021. We have included many factors, such as different geographical conditions (tropical climate, semitropic and arid conditions); GDP rate (developed nations, developing nations, and underdeveloped nations). We also categorized our data in order to conform to COVID-19 duration from 2019 to 2021. Data was extracted for the complete duration of 10 years (2012 to 2021) from various countries with different geographical region (arid region, semitropic/semiarid region and tropical region). RESULTS: There was a noticeable reduction in dengue cases in underdeveloped (70-85%), developing (50-90%), and developed nations (75%) in the years 2019 and 2021. The dengue cases drastically reduced by 55-65% with the advent of COVID-19 s wave in the year 2021 across the globe. CONCLUSIONS: At present, we can conclude that COVID-19 and dengue show an inverse relationship. These preliminary, data-based observations should guide clinical practice until more data are made public and basis for further medical research.

The integrative bioinformatics approaches to predict the xanthohumol as anti-breast cancer molecule: Targeting cancer cells signaling PI3K and AKT kinase pathway.

Background: Breast cancer is the most common type of cancer in women, and vast research is being conducted throughout the world for the treatment of this malignancy by natural products using various computational approaches. Xanthohumol, a prenylated flavonoid, is known for its anticancer activity; however, the mechanism behind its action is still in the preliminary stage. Methods: The current study aimed to analyze the efficacy of xanthohumol compared to the currently available anticancer drugs targeting phosphoinositide-3-kinase (PI3K), serine/threonine kinase (AKT) receptors, and human epidermal growth factor receptor 2 (HER2) for breast cancer treatment through in silico analysis. Results: The result revealed that the target compound showed significant binding affinity to targets within the PI3K, AKT, and HER2 signaling pathways with a binding energy of -7.5, -7.9, and -7.9 kcal/mol, respectively. Further prediction studies were then made concerning this compound's absorption, distribution, metabolism, and excretion (ADME) as well as drug-likeness properties, resulting in its oral bioavailability with only a single violation of Lipinski's rule of five. Conclusions: The finding revealed the ability of xanthohumol to bind with multiple cancer cell signaling molecules including PI3K, AKT kinase, and HER2. The current novel study opened the door to advancing research into the management and treatment of breast cancer.

Decipher the Helicobacter pylori Protein Targeting in the Nucleus of Host Cell and their Implications in Gallbladder Cancer: An insilico approach.

Gallbladder cancer (GBC) is one of the leading causes of cancer-related mortality worldwide. Researchers have investigated that specific strains of bacteria are connected with growth of different types of cancers in human. Some reports show possible implication of Helicobacter pylori (H. pylori) in the etiology of gallbladder cancer (GBC). Their enigmatic mechanisms, nevertheless, are not still well clear. We sought to predict whether various proteins of H. pylori targeted to nucleus of host cells and their implication in growth of gallbladder cancer. GBC is one of the leading causes of cancer mortality worldwide. We applied bioinformatics approach to analyze the H. pylori proteins targeting into the nucleus of host cells using different bioinformatics predictors including nuclear localization signal (NLS) mapper Balanced Subcellular Localization (BaCelLo) and Hum-mPLoc 2.0. Various nuclear targeting proteins may have a potential role in GBC etiology during intracellular infection. We identified 46 H. pylori proteins targeted into nucleus of host cell through bioinformatics tools. These H. pylori nucleus-targeting proteins might alter the normal function of host cells by disturbing the different pathways including replication, transcription, translation etc. Various nucleus-targeted proteins can affect the normal growth and development of infected cells. We propose that H. pylori proteins targeting into the nucleus of host cells regulate GBC growth using different strategies. These integrative bioinformatics research demonstrated several H. pylori proteins that may serve as possible targets or biomarkers for early cure and treatment or diagnosis GBC.

Chlamydia Trachomatis Infection: Their potential implication in the Etiology of Cervical Cancer.

Pathogenic bacterial strains can alter the normal function of cells and induce different levels of inflammatory responses that are connected to the development of different diseases, such as tuberculosis, diarrhea, cancer etc. Chlamydia trachomatis (C. trachomatis) is an intracellular obligate gram-negative bacterium which has been connected with the cervical cancer etiology. Nevertheless, establishment of causality and the underlying mechanisms of carcinogenesis of cervical cancer associated with C. trachomatis remain unclear. Studies reveal the existence of C. trachomatis in cervical cancer patients. The DNA repair pathways including mismatch repair, nucleotide excision, and base excision are vital in the abatement of accumulated mutations that can direct to the process of carcinogenesis. C. trachomatis recruits DDR proteins away from sites of DNA damage and, in this way, impedes the DDR. Therefore, by disturbing host cell-cycle control, chromatin and DDR repair, C. trachomatis makes a situation favorable for malignant transformation. Inflammation originated due to infection directs over production of reactive oxygen species (ROS) and consequent oxidative DNA damage. This review may aid our current understanding of the etiology of cervical cancer in C. trachomatis-infected patients.

Analysis of Salmonella typhimurium Protein-Targeting in the Nucleus of Host Cells and the Implications in Colon Cancer: An in-silico Approach.

BACKGROUND: Infections of Salmonella typhimurium (S. typhimurium) are major threats to health, threats include diarrhoea, fever, acute intestinal inflammation, and cancer. Nevertheless, little information is available about the involvement of S. typhimurium in colon cancer etiology. METHODS: The present study was designed to predict nuclear targeting of S. typhimurium proteins in the host cell through computational tools, including nuclear localization signal (NLS) mapper, Balanced Subcellular Localization predictor (BaCeILo), and Hum-mPLoc using next-generation sequencing data. RESULTS: Several gene expression-associated proteins of S. typhimurium have been predicted to target the host nucleus during intracellular infections. Nuclear targeting of S. typhimurium proteins can lead to competitive interactions between the host and pathogen proteins with similar cellular substrates, and it may have a possible involvement in colon cancer growth. Our results suggested that S. typhimurium releases its proteins within compartments of the host cell, where they act as a component of the host cell proteome. Protein targeting is possibly involved in colon cancer etiology during intracellular bacterial infection. CONCLUSION: The results of current in-silico study showed the potential involvement of S. typhimurium infection with alteration in normal functioning of host cell which act as possible factor to connect with the growth and development of colon cancer.

Highly Water-Soluble Luminescent Silica-Coated Cerium Fluoride Nanoparticles Synthesis, Characterizations, and In Vitro Evaluation of Possible Cytotoxicity.

A coprecipitation process was utilized for the preparation of terbium fluoride nanocrystals by cerium fluoride. Silica was used to modify the surface of these core/shell nanocrystals. The synthesized CeF3:Tb@LaF3 and CeF3:Tb@LaF3@SiO2 nanoparticles (NPs) were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), UV/vis spectrophotometry, and photoluminescence spectrophotometry. XRD patterns showed resolved reflection planes with broad widths, confirming the nanocrystalline nature of the CeF3:Tb@LaF3@SiO2 NPs. Fourier transform infrared spectra clearly revealed a uniform, smooth silica layer encapsulating the luminescent seed core and confirmed the polycrystalline nature of the CeF3:Tb@LaF3@SiO2 NPs. The TEM result showed an average crystalline size of 18 nm, which illustrated good agreement with the XRD results. The results of photoluminescence spectrophotometry confirmed the doping of terbium ions in the CeF3 crystal lattice. The cytotoxicity results of the MTT assay showed that CeF3:Tb@LaF3@SiO2 NPs have minimum toxicity with respect to CeF3:Tb@LaF3 NPs and the control drug dasatinib on HT-29 and HepG2 cell lines. Moreover, results of inverted microscopy confirmed the nontoxic and biocompatible nature of CeF3:Tb@LaF3@SiO2 NPs. These findings show that CeF3:Tb@LaF3@SiO2 NPs are promising candidates for applications in biomedical science in the future, such as bioimaging, biolabeling, biodetection or bio-probing, labeling of cells and tissue, drug delivery, cancer therapy, and multiplexed analysis.

Computational Proteome-Wide Study for the Prediction of Escherichia coli Protein Targeting in Host Cell Organelles and Their Implication in Development of Colon Cancer.

Enterohemorrhagic Escherichia coli infection is associated with gastrointestinal disorders, including diarrhea and colorectal cancer. Although evidences have established the involvement of E. coli in the growth of colon cancer, the molecular mechanisms of carcinogenesis of cancer growth and development are not well understood. We analyzed E. coli protein targeting in host cell organelles and the implication in colon cancer using in silico approaches. Our results indicated that many E. coli proteins targeted the endoplasmic reticulum (ER), ER membranes, Golgi apparatus, Golgi apparatus membranes, peroxisomes, nucleus, nuclear membrane, mitochondria, and mitochondrial membrane of host cells. These targeted proteins in ER, Golgi apparatus, peroxisomes, nucleus, and mitochondria may alter the normal functioning of various pathways including DNA repair, apoptosis, replication, transcription, and protein folding in E. coli-infected host cells. The results of the current in silico study provide insights into E. coli pathogenesis and may aid in designing new preventive and therapeutic strategies.

Biology, Pathophysiological Role, and Clinical Implications of Exosomes: A Critical Appraisal.

Exosomes are membrane-enclosed entities of endocytic origin, which are generated during the fusion of multivesicular bodies (MVBs) and plasma membranes. Exosomes are released into the extracellular milieu or body fluids; this process was reported for mesenchymal, epithelial, endothelial, and different immune cells (B-cells and dendritic cells), and was reported to be correlated with normal physiological processes. The compositions and abundances of exosomes depend on their tissue origins and cell types. Exosomes range in size between 30 and 100 nm, and shuttle nucleic acids (DNA, messenger RNAs (mRNAs), microRNAs), proteins, and lipids between donor and target cells. Pathogenic microorganisms also secrete exosomes that modulate the host immune system and influence the fate of infections. Such immune-modulatory effect of exosomes can serve as a diagnostic biomarker of disease. On the other hand, the antigen-presenting and immune-stimulatory properties of exosomes enable them to trigger anti-tumor responses, and exosome release from cancerous cells suggests they contribute to the recruitment and reconstitution of components of tumor microenvironments. Furthermore, their modulation of physiological and pathological processes suggests they contribute to the developmental program, infections, and human diseases. Despite significant advances, our understanding of exosomes is far from complete, particularly regarding our understanding of the molecular mechanisms that subserve exosome formation, cargo packaging, and exosome release in different cellular backgrounds. The present study presents diverse biological aspects of exosomes, and highlights their diagnostic and therapeutic potentials.