Nanomedicine as potential cancer therapy via targeting dysregulated transcription factors.

Cancer as a disease possess quite complicated pathophysiological implications and is among the prominent causes of morbidity and mortality on global scales. Anti-cancer chemotherapy, surgery, and radiation therapy are some of the present-day conventional treatment options. However, these therapeutic paradigms own several retreats, including lack of specificity, non-targeted toxicological implications, inefficient drug delivery to targeted cells, and emergence of cancer resistance, ultimately causing ineffective cancer management. Owing to the advanced and better biophysical characteristic features and potentiality for the tailoring and customizations and in several fashions, nanotechnology can entirely transubstantiate the cancer identification and its managements. Additionally, nanotechnology also renders several answers to present-day mainstream limitations springing-up in anti-cancer therapeutics. Nanocarriers, owing to their outstanding physicochemical features including but not limited to their particle size, surface morphological features viz. shape etc., have been employed in nanomedicinal platforms for targeting various transcription factors leading to worthy pharmacological outcomes. This transcription targeting activates the wide array of cellular and molecular events like antioxidant enzyme-induction, apoptotic cell death, cell-cycle arrest etc. These outcomes are obtained after the activation or inactivation of several transcription factors and cellular pathways. Further, nanoformulations have been precisely calibrated and functionalized with peculiar targeting groups for improving their efficiency to deliver the drug-payload to specified and targeted cancerous cells and tissues. This review undertakes an extensive, across-the-board and all-inclusive approach consisting of various studies encompassing different types of tailored and customized nanoformulations and nanomaterials designed for targeting the transcription factors implicated in the process of carcinogenesis, tumor-maturation, growth and metastasis. Various transcription factors viz. nuclear factor kappa (NF-κB), signal transducer and activators of transcription (STAT), Cmyc and Twist-related protein 1 (TWIST1) along with several types of nanoparticles targeting these transcription factors have been summarized here. A section has also been dedicated to the different types of nanoparticles targeting the hypoxia inducing factors. Efforts have been made to summarize several other transcription factors implicated in various stages of cancer development, growth, progression and invasion, and their targeting with different kinds of nanomedicinal agents.

The anti-staphylococcal fusidic acid as an efflux pump inhibitor combined with fluconazole against vaginal candidiasis in mouse model.

BACKGROUND: Candida albicans is the most common fungus that causes vaginal candidiasis in immunocompetent women and catastrophic infections in immunocompromised patients. The treatment of such infections is hindered due to the increasing emergence of resistance to azoles in C. albicans. New treatment approaches are needed to combat candidiasis especially in the dwindled supply of new effective and safe antifungals. The resistance to azoles is mainly attributed to export of azoles outside the cells by means of the efflux pump that confers cross resistance to all azoles including fluconazole (FLC). OBJECTIVES: This study aimed to investigate the possible efflux pump inhibiting activity of fusidic acid (FA) in C. albicans resistant isolates and the potential use of Fusidic acid in combination with fluconazole to potentiate the antifungal activity of fluconazole to restore its activity in the resistant C. albicans isolates. METHODS: The resistance of C. albicans isolates was assessed by determination of minimum inhibitory concentration. The effect of Fusidic acid at sub-inhibitory concentration on efflux activity was assayed by rhodamine 6G efflux assay and intracellular accumulation. Mice model studies were conducted to evaluate the anti-efflux activity of Fusidic acid and its synergistic effects in combination with fluconazole. Impact of Fusidic acid on ergosterol biosynthesis was quantified. The synergy of fluconazole when combined with Fusidic acid was investigated by determination of minimum inhibitory concentration. The cytotoxicity of Fusidic acid was tested against erythrocytes. The effect of Fusidic acid on efflux pumps was tested at the molecular level by real-time PCR and in silico study. In vivo vulvovaginitis mice model was used to confirm the activity of the combination in treating vulvovaginal candidiasis. RESULTS: Fusidic acid showed efflux inhibiting activity as it increased the accumulation of rhodamine 6G, a substrate for ABC-efflux transporter, and decreased its efflux in C. albicans cells. The antifungal activity of fluconazole was synergized when combined with Fusidic acid. Fusidic acid exerted only minimal cytotoxicity on human erythrocytes indicating its safety. The FA efflux inhibitory activity could be owed to its ability to interfere with efflux protein transporters as revealed by docking studies and downregulation of the efflux-encoding genes of both ABC transporters and MFS superfamily. Moreover, in vivo mice model showed that using fluconazole-fusidic acid combination by vaginal route enhanced fluconazole antifungal activity as shown by lowered fungal burden and a negligible histopathological change in vaginal tissue. CONCLUSION: The current findings highlight FA's potential as a potential adjuvant to FLC in the treatment of vulvovaginal candidiasis.

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.

Antiangiogenic potential of phytochemicals from Clerodendrum inerme (L.) Gaertn investigated through in silico and quantum computational methods.

Suppressing vascular endothelial growth factor (VEGF), its receptor (VEGFR2), and the VEGF/VEGFR2 signaling cascade system to inhibit angiogenesis has emerged as a possible cancer therapeutic target. The present work was designed to discover and evaluate bioactive phytochemicals from the Clerodendrum inerme (L.) Gaertn plant for their anti-angiogenic potential. Molecular docking of twenty-one phytochemicals against the VEGFR-2 (PDB ID: 3VHE) protein was performed, followed by ADMET profiling and molecular docking simulations. These investigations unveiled two hit compounds, cirsimaritin (- 12.29 kcal/mol) and salvigenin (- 12.14 kcal/mol), with the highest binding energy values when compared to the reference drug, Sorafenib (- 15.14 kcal/mol). Furthermore, only nine phytochemicals (cirsimaritin and salvigenin included) obeyed Lipinski's rule of five and passed ADMET filters. Molecular dynamics simulations run over 100 ns revealed that the protein-ligand complexes remained stable with minimal backbone fluctuations. The binding free energy values of cirsimaritin (- 52.35 kcal/mol) and salvigenin (- 55.89 kcal/mol), deciphered by MM-GBSA analyses, further corroborated the docking interactions. The HOMO-LUMO band energy gap (ΔE) was calculated using density-functional theory (DFT) and substantiated using density of state (DOS) spectra. The chemical reactivity analyses revealed that salvigenin exhibited the highest chemical softness value (6.384 eV), the lowest hardness value (0.07831 eV), and the lowest ΔE value (0.1566 eV), which implies salvigenin was less stable and chemically more reactive than cirsimaritin and sorafenib. These findings provide further evidence that cirsimaritin and salvigenin have the ability to prevent angiogenesis and the development of cancer. Nevertheless, more in vitro and in vivo confirmation is necessary.

Functionalized-DNA nanostructures as potential targeted drug delivery systems for cancer therapy.

Seeman's pioneer idea has led to the foundation of DNA nanostructures, resulting in a remarkable advancement in DNA nanotechnology. Over the last few decades, remarkable advances in drug delivery techniques have resulted in the self-assembly of DNA for encapsulating candidate drug molecules. The nuclear targeting capability of DNA nanostructures is lies within their high spatial addressability and tremendous potential for active targeting. However, effective programming and assembling those DNA molecules remains a challenge, making the path to DNA nanostructures for real-world applications difficult. Because of their small size, most nanostructures are self-capable of infiltrating into the tumor cellular environment. Furthermore, to enable controlled and site-specific delivery of encapsulated drug molecules, DNA nanostructures are functionalized with special moieties that allow them to bind specific targets and release cargo only at targeted sites rather than non-specific sites, resulting in the prevention/limitation of cellular toxicity. In light of this, the current review seeks to shed light on the versatility of the DNA molecule as a targeting and encapsulating moiety for active drugs in order to achieve controlled and specific drug release with spatial and temporal precision. Furthermore, this review focused on the challenges associated with the construction of DNA nanostructures as well as the most recent advances in the functionalization of DNA nanostructures using various materials for controlled and targeted delivery of medications for cancer therapy.

MicroRNAs: Small molecules with big impacts in liver injury.

A type of small noncoding RNAs known as microRNAs (miRNAs) fine-tune gene expression posttranscriptionally by binding to certain messenger RNA targets. Numerous physiological processes in the liver, such as differentiation, proliferation, and apoptosis, are regulated by miRNAs. Additionally, there is growing evidence that miRNAs contribute to liver pathology. Extracellular vesicles like exosomes, which contain secreted miRNAs, may facilitate paracrine and endocrine communication between various tissues by changing the gene expression and function of distal cells. The use of stable miRNAs as noninvasive biomarkers was made possible by the discovery of these molecules in body fluids. Circulating miRNAs reflect the conditions of the liver that are abnormal and may serve as new biomarkers for the early detection, prognosis, and evaluation of liver pathological states. miRNAs are appealing therapeutic targets for a range of liver disease states because altered miRNA expression is associated with deregulation of the liver's metabolism, liver damage, liver fibrosis, and tumor formation. This review provides a comprehensive review and update on miRNAs biogenesis pathways and mechanisms of miRNA-mediated gene silencing. It also outlines how miRNAs affect hepatic cell proliferation, death, and regeneration as well as hepatic detoxification. Additionally, it highlights the diverse functions that miRNAs play in the onset and progression of various liver diseases, including nonalcoholic fatty liver disease, alcoholic liver disease, fibrosis, hepatitis C virus infection, and hepatocellular carcinoma. Further, it summarizes the diverse liver-specific miRNAs, illustrating the potential merits and possible caveats of their utilization as noninvasive biomarkers and appealing therapeutic targets for liver illnesses.

Complexity of Tumor Microenvironment: Therapeutic Role of Curcumin and Its Metabolites.

The tumor microenvironment (TME) is a complex network of cellular and non-cellular components surrounding the tumor. The cellular component includes fibroblasts, adipocytes, endothelial cells, and immune cells, while non-cellular components are tumor vasculature, extracellular matrix and signaling molecules. The tumor cells have constant close interaction with their surrounding TME components that facilitate their growth, survival, and metastasis. Targeting a complex TME network and its interaction with the tumor can offer a novel strategy to disrupt cancer cell progression. Curcumin, from turmeric rhizome, is recognized as a safe and effective natural therapeutic agent against multiple diseases including cancer. Here the effects of curcumin and its metabolites on tumor-TME interaction modulating ability have been described. Curcumin and its metabolites regulate TME by inhibiting the growth of its cellular components such as cancer-associated adipocytes, cancer-associated fibroblast, tumor endothelial cells, tumor-stimulating immune cells, and inducing anticancer immune cells. They also inhibit the interplay of tumor cells to TME by suppressing non-cellular components such as extracellular matrix, and associated tumor promoting signaling-pathways. In addition, curcumin inhibits the inflammatory environment, suppresses angiogenic factors, and increases antioxidant status in TME. Overall, curcumin has the capability to regulate TME components and their interaction with tumor cells.

Nanostructured material-based optical and electrochemical detection of amoxicillin antibiotic.

The penicillin derivative amoxicillin (AMX) plays an important role in treating various types of infections caused by bacteria. However, excessive use of AMX may have negative health effects. Therefore, it is of utmost importance to detect and quantify the AMX in pharmaceutical drugs, biological fluids, and environmental samples with high sensitivity. Therefore, this review article provides valuable and up-to-date information on nanostructured material-based optical and electrochemical sensors to detect AMX in various biological and chemical samples. The role of using different nanostructured materials on the performance of important optical sensors such as colorimetric sensors, fluorescence sensors, surface-enhanced Raman scattering sensors, chemiluminescence/electroluminescence sensors, optical immunosensors, optical fibre-based sensors, and several important electrochemical sensors based on different electrode types have been discussed. Moreover, nanocomposites, polymer, and MXenes-based electrochemical sensors have also been discussed, in which such materials are being used to further enhance the sensitivity of these sensors. Furthermore, nanocomposite-based photo-electrochemical sensors and the market availability of biosensors including AMX have also been discussed briefly. Finally, the conclusion, challenges, and future perspectives of the above-mentioned sensing techniques for AMX detection are presented.

Wildfire-induced pollution and its short-term impact on COVID-19 cases and mortality in California.

Globally, wildfires have seen remarkable increase in duration and size and have become a health hazard. In addition to vegetation and habitat destruction, rapid release of smoke, dust and gaseous pollutants in the atmosphere contributes to its short and long-term detrimental effects. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged as a public health concern worldwide that primarily target lungs and respiratory tract, akin to air pollutants. Studies from our lab and others have demonstrated association between air pollution and COVID-19 infection and mortality rates. However, current knowledge on the impact of wildfire-mediated sudden outburst of air pollutants on COVID-19 is limited. In this study, we examined the association of air pollutants and COVID-19 during wildfires burned during August-October 2020 in California, United States. We observed an increase in the tropospheric pollutants including aerosols (particulate matter [PM]), carbon monoxide (CO) and nitrogen dioxide (NO2) by approximately 150%, 100% and 20%, respectively, in 2020 compared to the 2019. Except ozone (O3), similar proportion of increment was noticed during the peak wildfire period (August 16 - September 15, 2020) in the ground PM2.5, CO, and NO2 levels at Fresno, Los Angeles, Sacramento, San Diego and San Francisco, cities with largest active wildfire area. We identified three different spikes in the concentrations of PM2.5, and CO for the cities examined clearly suggesting wildfire-induced surge in air pollution. Fresno and Sacramento showed increment in the ground PM2.5, CO and NO2 levels, while San Diego recorded highest change rate in NO2 levels. Interestingly, we observed a similar pattern of higher COVID-19 cases and mortalities in the cities with adverse air pollution caused by wildfires. These findings provide a logical rationale to strategize public health policies for future impact of COVID-19 on humans residing in geographic locations susceptible to sudden increase in local air pollution.

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.

Iron Oxide Nanoparticle-Based Ferro-Nanofluids for Advanced Technological Applications.

Iron oxide nanoparticle (ION)-based ferro-nanofluids (FNs) have been used for different technological applications owing to their excellent magneto-rheological properties. A comprehensive overview of the current advancement of FNs based on IONs for various engineering applications is unquestionably necessary. Hence, in this review article, various important advanced technological applications of ION-based FNs concerning different engineering fields are critically summarized. The chemical engineering applications are mainly focused on mass transfer processes. Similarly, the electrical and electronics engineering applications are mainly focused on magnetic field sensors, FN-based temperature sensors and tilt sensors, microelectromechanical systems (MEMS) and on-chip components, actuators, and cooling for electronic devices and photovoltaic thermal systems. On the other hand, environmental engineering applications encompass water and air purification. Moreover, mechanical engineering or magneto-rheological applications include dampers and sealings. This review article provides up-to-date information related to the technological advancements and emerging trends in ION-based FN research concerning various engineering fields, as well as discusses the challenges and future perspectives.

FNDC5/Irisin: Physiology and Pathophysiology.

A sedentary lifestyle or lack of physical activity increases the risk of different diseases, including obesity, diabetes, heart diseases, certain types of cancers, and some neurological diseases. Physical exercise helps improve quality of life and reduces the risk of many diseases. Irisin, a hormone induced by exercise, is a fragmented product of FNDC5 (a cell membrane protein) and acts as a linkage between muscles and other tissues. Over the past decade, it has become clear that irisin is a molecular mimic of exercise and shows various beneficial effects, such as browning of adipocytes, modulation of metabolic processes, regulation of bone metabolism, and functioning of the nervous system. Irisin has a role in carcinogenesis; numerous studies have shown its impact on migration, invasion, and proliferation of cancer cells. The receptor of irisin is not completely known; however, in some tissues it probably acts via a specific class of integrin receptors. Here, we review research from the past decade that has identified irisin as a potential therapeutic agent in the prevention or treatment of various metabolic-related and other diseases. This article delineates structural and biochemical aspects of irisin and provides an insight into the role of irisin in different pathological conditions.

Elucidating the Role of Santalol as a Potent Inhibitor of Tyrosinase: In Vitro and In Silico Approaches.

This research work focuses on the potential application of an organic compound, santalol, obtained from santalum album, in the inhibition of the enzyme tyrosinase, which is actively involved in the biosynthesis of melanin pigment. Over-production of melanin causes undesirable pigmentation in humans as well as other organisms and significantly downgrades their aesthetic value. The study is designed to explain the purification of tyrosinase from the mushroom Agaricus bisporus, followed by activity assays and enzyme kinetics to give insight into the santalol-modulated tyrosinase inhibition in a dose-dependent manner. The multi-spectroscopic techniques such as UV-vis, fluorescence, and isothermal calorimetry are employed to deduce the efficiency of santalol as a potential candidate against tyrosinase enzyme activity. Experimental results are further verified by molecular docking. Santalol, derived from the essential oils of santalum album, has been widely used as a remedy for skin disorders and a potion for a fair complexion since ancient times. Based on enzyme kinetics and biophysical characterization, this is the first scientific evidence where santalol inhibits tyrosinase, and santalol may be employed in the agriculture, food, and cosmetic industries to prevent excess melanin formation or browning.

Jeopardy of COVID-19: Rechecking the Perks of Phytotherapeutic Interventions.

The novel coronavirus disease (COVID-19), the reason for worldwide pandemic, has already masked around 220 countries globally. This disease is induced by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Arising environmental stress, increase in the oxidative stress level, weak immunity and lack of nutrition deteriorates the clinical status of the infected patients. Though several researches are at its peak for understanding and bringing forward effective therapeutics, yet there is no promising solution treating this disease directly. Medicinal plants and their active metabolites have always been promising in treating many clinical complications since time immemorial. Mother nature provides vivid chemical structures, which act multi-dimensionally all alone or synergistically in mitigating several diseases. Their unique antioxidant and anti-inflammatory activity with least side effects have made them more effective candidate for pharmacological studies. These medicinal plants inhibit attachment, encapsulation and replication of COVID-19 viruses by targeting various signaling molecules such as angiotensin converting enzyme-2, transmembrane serine protease 2, spike glycoprotein, main protease etc. This property is re-examined and its potency is now used to improve the existing global health crisis. This review is an attempt to focus various antiviral activities of various noteworthy medicinal plants. Moreover, its implications as prophylactic or preventive in various secondary complications including neurological, cardiovascular, acute kidney disease, liver disease are also pinpointed in the present review. This knowledge will help emphasis on the therapeutic developments for this novel coronavirus where it can be used as alone or in combination with the repositioned drugs to combat COVID-19.

Bacterial imbalance and gut pathologies: Association and contribution of E. coli in inflammatory bowel disease.

Hosts and microbes have co-evolved over millions of years. Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated diseases. Although the etiology of IBD remains an enigma, various studies have proposed the involvement of mucosa-associated Escherichia coli (E. coli) strains in the pathogenesis of IBD. E. coli, a usual inhabitant of the intestine, causes disease after acquiring virulence factors; however, the mechanisms underlying this phenomenon are not well understood. In the present review, we will discuss recent findings on how gut E. coli regulates and controls gut homeostasis and the pathogenesis of IBD. We will also summarize current knowledge regarding the cause, mechanism, genetics, and environmental factors involved in the regulation of IBD. Furthermore, we will discuss the possibility of alterations in innate and acquired immunity during the course of disease as well as possible treatment.

Global prevalence and distribution of coinfection of malaria, dengue and chikungunya: a systematic review.

BACKGROUND: Malaria, Dengue and Chikungunya are vector borne diseases with shared endemic profiles and symptoms. Coinfections with any of these diseases could have fatal outcomes if left undiagnosed. Understanding the prevalence and distribution of coinfections is necessary to improve diagnosis and designing therapeutic interventions. METHODS: We have carried out a systematic search of the published literature based on PRISMA guidelines to identify cases of Malaria, Dengue and Chikungunya coinfections. We systematically reviewed the literature to identify eligible studies and extracted data regarding cases of coinfection from cross sectional studies, case reports, retrospective studies, prospective observational studies and surveillance reports. RESULTS: Care full screening resulted in 104 publications that met the eligibility criteria and reported Malaria/Dengue, Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. These coinfections were spread over six geographical locations and 42 different countries and are reported more frequently in the last 15 years possibly due to expanding epidemiology of Dengue and Chikungunya. Few of these reports have also analysed distinguishing features of coinfections. Malaria/Dengue coinfections were the most common coinfection followed by Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. P. falciparum and P. vivax were the commonest species found in cases of malaria coinfections and Dengue serotype-4 commonest serotype in cases of dengue coinfections. Most studies were reported from India. Nigeria and India were the only two countries from where all possible combinations of coinfections were reported. CONCLUSION: We have comprehensively reviewed the literature associated with cases of coinfections of three important vector borne diseases to present a clear picture of their prevalence and distribution across the globe. The frequency of coinfections presented in the study suggests proper diagnosis, surveillance and management of cases of coinfection to avoid poor prognosis of the underlying etiology.

To Decipher the Mycoplasma hominis Proteins Targeting into the Endoplasmic Reticulum and Their Implications in Prostate Cancer Etiology Using Next-Generation Sequencing Data.

Cancer was initially considered a genetic disease. However, recent studies have revealed the connection between bacterial infections and growth of different types of cancer. The enteroinvasive strain of Mycoplasma hominis alters the normal behavior of host cells that may result in the growth of prostate cancer. The role of M. hominis in the growth and development of prostate cancer still remains unclear. The infection may regulate several factors that influence prostate cancer growth in susceptible individuals. The aim of this study was to predict M. hominis proteins targeted into the endoplasmic reticulum (ER) of the host cell, and their potential role in the induction of prostate cancer. From the whole proteome of M. hominis, 19 proteins were predicted to be targeted into the ER of host cells. The results of our study predict that several proteins of M. hominis may be targeted to the host cell ER, and possibly alter the normal pattern of protein folding. These predicted proteins can modify the normal function of the host cell. Thus, the intercellular infection of M. hominis in host cells may serve as a potential factor in prostate cancer etiology.

Anti-diabetic potential of Catharanthus roseus Linn. and its effect on the glucose transport gene (GLUT-2 and GLUT-4) in streptozotocin induced diabetic wistar rats.

BACKGROUND: Catharanthus roseus is an important Ayurvedic medication in traditional medicine. It is potentially used in countries like India, South Africa, China and Malaysia for the healing of diabetes mellitus. Although, the molecular mechanisms behind this effect are yet to be exclusively explored. Due to the great antidiabetic and hyperlipidemic potential of c. roseus, we hypothesized that the insulin mimetic effect of ethanolic extract of c. roseus might add to glucose uptake through improvement in the expression of genes of the glucose transporter (GLUT) family messenger RNA (mRNA) in liver. METHODS: STZ-induced diabetic rats treated by ethanolic extract of c. roseus 100 mg/kg and 200 mg/kg; and one group treated with Metformin (100 mg/kg). After final administration of treatment of 4 weeks, blood samples were collected under fasting conditions, and the body weights (BWs) were measured. Total RNA from liver was extracted with the Qiagen RNEasy Micro kit (GERMANY) as described in the manufacturer's instructions. First-strand complementary DNA (cDNA) was synthesized at 40 °C by priming with oligo-dT12-18 (Invitrogen, USA) and using Super ScriptII reverse transcriptase according to the protocol provided by the manufacturer (Invitrogen, USA). Real-time polymerase chain reaction (PCR) amplifications for GLUT-4 (gene ID: 25139) were conducted using Light-Cycler 480 (Roche, USA) with the SyBr® I nucleic acid stain (Invitrogen, USA) according to the manufacturer's instructions. Polymerase chain reaction products of ß-actin primer gene were used as an internal standard. RESULTS: The proposed study was framed to look at the antidiabetic efficacy of ethanolic extract of c. roseus and an expression of GLUT-2 and GLUT-4 gene in streptozotocin induced diabetic wistar rats. The doses were administered orally at a rate of 100 and 200 mg/kg and detrain the glucose transport system in liver for 4 weeks. The observed results showed a good positive correlation between intracellular calcium and insulin release levels in isolated islets of Langerhans. The supplementation of ethanolic extract of c. roseus significantly amplified the expression of GLUT gene mRNA by Real Time PCR in liver of diabetic rats. CONCLUSIONS: We conclude that the observed antidiabetic effect of c. roseus on STZ induced diabetes was a result of complex mechanisms of GLUT gene mRNA expression. The findings are very encouraging and greatly advocate its candidature for the design of a novel herbal drug to cure deadly diabetes.

Amyloid-induced neurodegeneration: A comprehensive review through aggregomics perception of proteins in health and pathology.

Amyloidosis of protein caused by fibrillation and aggregation are some of the most exciting new edges not only in protein sciences but also in molecular medicines. The present review discusses recent advancements in the field of neurodegenerative diseases and therapeutic applications with ongoing clinical trials, featuring new areas of protein misfolding resulting in aggregation. The endogenous accretion of protein fibrils having fibrillar morphology symbolizes the beginning of neuro-disorders. Prognostic amyloidosis is prominent in numerous degenerative infections such as Alzheimer's and Parkinson's disease, Amyotrophic lateral sclerosis (ALS), etc. However, the molecular basis determining the intracellular or extracellular evidence of aggregates, playing a significant role as a causative factor in neurodegeneration is still unclear. Structural conversions and protein self-assembly resulting in the formation of amyloid oligomers and fibrils are important events in the pathophysiology of the disease. This comprehensive review sheds light on the evolving landscape of potential treatment modalities, highlighting the ongoing clinical trials and the potential socio-economic impact of novel therapeutic interventions in the realm of neurodegenerative diseases. Furthermore, many drugs are undergoing different levels of clinical trials that would certainly help in treating these disorders and will surely improve the socio-impact of human life.

A Retrospective Exploration of Pre-operative Antibiotic Prophylaxis with Cefazolin in Cesarean Sections: Implications for Obstetrics and Gynecologic Surgery.

Background: Post-partum infection is a major contributor to maternal mortality and is responsible for approximately 10% of maternal fatalities worldwide. The risk of infection is substantially higher in cesarean section procedures. Approximately 8% of women who undergo cesarean sections are susceptible to infection. Although the body of evidence supporting the regular pre-operative utilization of prophylactic antibiotic treatment is steadily expanding, its usefulness in cesarean sections has not yet been standardized, and post-partum infection is still a serious medical challenge. We aimed to retrospectively assess the prophylactic effectiveness of cefazolin in combination with other antibiotic agents in cesarean sections. Materials and Methods: Both uni-variable and multi-variable analyses were conducted to identify factors that may affect cefazolin pre-operative antibiotic prophylaxis in elective cesarean section operations. The uni-variable analysis included timing of administration, operation duration, body mass index (BMI), and wound type. A multi-variable logistic regression model was then created to determine which variables provide independent information in the context of other variables. Results: Time of administration did not affect prophylactic cefazolin efficacy. However, prophylactic cefazolin was 1.43 and 1.77 times more effective when the operation lasted for 45 minutes or more, compared with operations that were shorter than 45 minutes. Patients with a BMI ranging from 18 to 29 kg/m2 showed increased efficacy of prophylactic cefazolin compared with obese patients with a BMI exceeding 30 kg/m2. The effectiveness of prophylactic cefazolin decreased by 95% in patients with clean-contaminated surgical incisions compared with those with clean surgical incisions. Conclusions: Our findings demonstrate that administering pre-operative prophylactic antibiotic agents to women undergoing cesarean section resulted in a reduction in post-partum infections, thereby reducing maternal mortality. Furthermore, optimal timing of administration, re-dosing if necessary, length of prophylactic medication, and dosing adjustments for obese patients are crucial factors in preventing surgical site infections and promoting antimicrobial stewardship.