Exploration of gut microbiome and inflammation: A review on key signalling pathways.

The gut microbiome, a crucial component of the human system, is a diverse collection of microbes that belong to the gut of human beings as well as other animals. These microbial communities continue to coexist harmoniously with their host organisms and perform various functions that affect the host's general health. Each person's gut microbiota has a unique makeup. The gut microbiota is well acknowledged to have a part in the local as well as systemic inflammation that underlies a number of inflammatory disorders (e.g., atherosclerosis, diabetes mellitus, obesity, and inflammatory bowel disease).The gut microbiota's metabolic products, such as short-chain fatty acids (butyrate, propionate, and acetate) inhibit inflammation by preventing immune system cells like macrophages and neutrophils from producing pro-inflammatory factors, which are triggered by the structural elements of bacteria (like lipopolysaccharide). The review's primary goal is to provide comprehensive and compiled data regarding the contribution of gut microbiota to inflammation and the associated signalling pathways.

Comparative Genome Analysis of Old World and New World TYLCV Reveals a Biasness toward Highly Variable Amino Acids in Coat Protein.

Begomoviruses, belonging to the family Geminiviridae and the genus Begomovirus, are DNA viruses that are transmitted by whitefly Bemisia tabaci (Gennadius) in a circulative persistent manner. They can easily adapt to new hosts and environments due to their wide host range and global distribution. However, the factors responsible for their adaptability and coevolutionary forces are yet to be explored. Among BGVs, TYLCV exhibits the broadest range of hosts. In this study, we have identified variable and coevolving amino acid sites in the proteins of Tomato yellow leaf curl virus (TYLCV) isolates from Old World (African, Indian, Japanese, and Oceania) and New World (Central and Southern America). We focused on mutations in the coat protein (CP), as it is highly variable and interacts with both vectors and host plants. Our observations indicate that some mutations were accumulating in Old World TYLCV isolates due to positive selection, with the S149N mutation being of particular interest. This mutation is associated with TYLCV isolates that have spread in Europe and Asia and is dominant in 78% of TYLCV isolates. On the other hand, the S149T mutation is restricted to isolates from Saudi Arabia. We further explored the implications of these amino acid changes through structural modeling. The results presented in this study suggest that certain hypervariable regions in the genome of TYLCV are conserved and may be important for adapting to different host environments. These regions could contribute to the mutational robustness of the virus, allowing it to persist in different host populations.

Evaluation of the association of chronic inflammation and cancer: Insights and implications.

Among the most extensively researched processes in the development and treatment of cancer is inflammatory condition. Although acute inflammation is essential for the wound healing and reconstruction of tissues that have been damaged, chronic inflammation may contribute to the onset and growth of a number of diseases, including cancer. By disrupting the signaling processes of cells, which result in cancer induction, invasion, and development, a variety of inflammatory molecules are linked to the development of cancer. The microenvironment surrounding the tumor is greatly influenced by inflammatory cells and their subsequent secretions, which also contribute significantly to the tumor's growth, survivability, and potential migration. These inflammatory variables have been mentioned in several publications as prospective diagnostic tools for anticipating the onset of cancer. Targeting inflammation with various therapies can reduce the inflammatory response and potentially limit or block the proliferation of cancer cells. The scientific medical literature from the past three decades has been studied to determine how inflammatory chemicals and cell signaling pathways related to cancer invasion and metastasis are related. The current narrative review updates the relevant literature while highlighting the specifics of inflammatory signaling pathways in cancer and their possible therapeutic possibilities.

Role of the Dietary Phytochemical Curcumin in Targeting Cancer Cell Signalling Pathways.

The diarylheptanoid curcumin [(1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione] is one of the phenolic pigments responsible for the yellow colour of turmeric (Curcuma longa L.). This phytochemical has gained much attention in recent years due to its therapeutic potential in cancer. A range of drug delivery approaches have been developed to optimise the pharmacokinetic profile of curcumin and ensure that it reaches its target sites. Curcumin exhibits numerous biological effects, including anti-inflammatory, cardioprotective, antidiabetic, and anti-aging activities. It has also been extensively studied for its role as a cancer chemopreventive and anticancer agent. This review focusses on the role of curcumin in targeting the cell signalling pathways involved in cancer, particularly via modulation of growth factors, transcription factors, kinases and other enzymes, pro-inflammatory cytokines, and pro-apoptotic and anti-apoptotic proteins. It is hoped that this study will help future work on the potential of curcumin to fight cancer.

Impact of COVID-19 Pandemic on Older Adults Using Hearing aid/s: Indian Scenario.

The present study explored the impact of COVID-19 on hearing health and problems faced by older adults using hearing aid/s. Fifty older adults in the age range of 55-95 years were selected for the study based on the inclusion and exclusion criteria. Therefore, the developed questionnaire was administered to them. Statistical analysis was performed for all the responses achieved. Closure of hearing aid companies and audiological centers was found to have a negative impact on availing audiological services. Likewise, a huge hike in the price of these services made it impossible for people to afford them. Despite the availability of tele-audiology, older adults were not able to make the best use of it due to numerous reasons. We sought to explore patients' perceptions to break down these barriers by enhancing the quality of tele-audiology, home visits, and remote services. Therefore, the present report may facilitate in planning and implementation of policies related to audiological services, especially during times of crisis, which may help strengthen our hearing health care system. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03209-8.

Revisiting scrub typhus: A neglected tropical disease.

Scrub typhus is an under diagnosed re-emerging vector borne disease caused by an intracellular gram negative bacteria, Orientia. The disease is commonly prevalent in rural and hilly areas of Tsutsugumashi triangle. The diagnosis of the disease is very challenging due to similarity of its early symptoms with other febrile illnesses, like dengue and COVID 19, as well as non-availability of rapid, reliable and cost-effective methods. Moreover, the diverse clinical presentation in severe cases make it significant health problem. The occupational and behavioral risks responsible for the transmission lead to urgent need of vaccine development against the disease. The complete knowledge about its pathogenesis and the interaction with host's immune cells may help the scientists in developing the appropriate diagnostic methods as well as the vaccines.

Orchestrating the fecal microbiota transplantation: Current technological advancements and potential biomedical application.

Fecal microbiota transplantation (FMT) has been proved to be an effective treatment for gastrointestinal disorders caused due to microbial disbalance. Nowadays, this approach is being used to treat extragastrointestinal conditions like metabolic and neurological disorders, which are considered to have their provenance in microbial dysbiosis in the intestine. Even though case studies and clinical trials have demonstrated the potential of FMT in treating a variety of ailments, safety and ethical concerns must be answered before the technique is widely used to the community's overall benefit. From this perspective, it is not unexpected that techniques for altering gut microbiota may represent a form of medication whose potential has not yet been thoroughly addressed. This review intends to gather data on recent developments in FMT and its safety, constraints, and ethical considerations.

Cancer Stem Cells: From an Insight into the Basics to Recent Advances and Therapeutic Targeting.

Cancer is characterized by an abnormal growth of the cells in an uncontrolled manner. These cells have the potential to invade and can eventually turn into malignancy, leading to highly fatal forms of tumor. Small subpopulations of cancer cells that are long-lived with the potential of excessive self-renewal and tumor formation are called cancer stem cells (CSCs) or cancer-initiating cells or tumor stem cells. CSCs can be found in tissues, such as breast, brain, lung, liver, ovary, and testis; however, their origin is still a matter of debate. These cells can differentiate and possess self-renewal capacity maintained by numerous intracellular signal transduction pathways, such as the Wnt/ß-catenin signaling, Notch signaling, transforming growth factor-ß signaling, and Hedgehog signaling. They can also contribute to numerous malignancies and are an important reason for tumor recurrence and metastasis because they are resistant to the known therapeutic strategies that mainly target the bulk of the tumor cells. This review contains collected and compiled information after analyzing published works of the last three decades. The goal was to gather information of recent breakthroughs related to CSCs, strategies to target CSCs' niche (e.g., nanotechnology with tumor biology), and their signaling pathways for cancer therapy. Moreover, the role of metformin, an antidiabetic drug, acting as a chemotherapeutic agent on CSCs by inhibiting cellular transformation and its selective killing is also addressed.

Cancer and diabetes: the interlinking metabolic pathways and repurposing actions of antidiabetic drugs.

Cancers are regarded as one of the main causes of death and result in high health burden worldwide. The management of cancer include chemotherapy, surgery and radiotherapy. The chemotherapy, which involves the use of chemical agents with cytotoxic actions is utilised as a single treatment or combined treatment. However, these managements of cancer such as chemotherapy poses some setbacks such as cytotoxicity on normal cells and the problem of anticancer drug resistance. Therefore, the use of other therapeutic agents such as antidiabetic drugs is one of the alternative interventions used in addressing some of the limitations in the use of anticancer agents. Antidiabetic drugs such as sulfonylureas, biguanides and thiazolidinediones showed beneficial and repurposing actions in the management of cancer, thus, the activities of these drugs against cancer is attributed to some of the metabolic links between the two disorders and these includes hyperglycaemia, hyperinsulinemia, inflammation, and oxidative stress as well as obesity. Furthermore, some studies showed that the use of antidiabetic drugs could serve as risk factors for the development of cancerous cells particularly pancreatic cancer. However, the beneficial role of these chemical agents overweighs their detrimental actions in cancer management. Hence, the present review indicates the metabolic links between cancer and diabetes and the mechanistic actions of antidiabetic drugs in the management of cancers.

Antibacterial activity and phytochemical characterisation of Saussurea gossypiphora D. Don.

The study demonstrates that S. gossypiphora contain number of secondary metabolites such as steroids, tannins, flavonoids, phenolics, carbohydrates, saponins, and amino acids. Methanolic extract (MESG) of the plant contained highest quantity of phenolics, flavonoids and has greater antioxidant, anti-inflammatory and antibacterial activity in comparison to other extracts. Moreover, acute toxicity studies revealed that none of the extracts produced any toxic symptoms and mortality when administered orally to mice at a dose of 2000 mg/kg b. w. Furthermore, in MESG, the SG-4 fraction exhibited the highest antibacterial activity than other isolated fractions against all tested bacterial strains in a dose-dependent manner. SG-4 fraction showed significant anti-inflammatory effect (60.91%) as evident by maximum inhibition of Carrageenan-induced paw oedema in rat model. The HPTLC analysis confirmed the presence of apigenin and luteolin in the SG-4 fraction of methanolic extract. A noticeable number of mineral elements were also found to be present in S. gossypiphora. Conclusively, our study reveals that Saussurea gossypiphora contains plethora of bioactive compounds that contributes to its antioxidant, anti-inflammatory and antibacterial activity. Apigenin and luteolin possibly being one of them. Besides, the presence of ample minerals hints is utilisation as nutritionally valuable herb.

Micro-RNA: The darkhorse of cancer.

The discovery of micro RNAs (miRNA) in cancer has opened up new vistas for researchers in recent years. Micro RNAs area set of small, endogenous, highly conserved, non-coding RNAs that control the expression of about 30% genes at post-transcriptional levels. Typically, microRNAs impede the translation and stability of messenger RNAs (mRNA), control genes associated with cellular processes namely inflammation, cell cycle regulation, stress response, differentiation, apoptosis, and migration. Compelling findings revealed that miRNA mutations or disruption correspond to diverse human cancers and suggest that miRNAs can function as tumor suppressors or oncogenes. Here we summarize the literature on these master regulators in clinical settings from last three decades as both abrupt cancer therapeutics and as an approach to sensitize tumors to chemotherapy. This review highlights (I) the prevailing perception of miRNA genomics, biogenesis, as well as function; (II) the significant advancements in regulatory mechanisms in the expression of carcinogenic genes; and (III) explains, how miRNA is utilized as a diagnostic and prognostic biomarker for the disease stage indicating survival as well as therapeutic targets in cancer.

Ficus plants: State of the art from a phytochemical, pharmacological, and toxicological perspective.

Ficus genus is typically tropical plants and is among the earliest fruit trees cultivated by humans. Ficus carica L. is the common fig, Ficus benjamina L. is the weeping fig, and Ficus pumila L. is the creeping fig. These species are commonly used in traditional medicine for a wide range of diseases and contain rich secondary metabolites that have shown diverse applications. This comprehensive review describes for Ficus genus the phytochemical compounds, traditional uses and contemporary pharmacological activities such as antioxidant, cytotoxic, antimicrobial, anti-inflammatory, antidiabetic, antiulcer, and anticonvulsant. An extended survey of the current literature (Science Direct, Scopus, PubMed) has been carried out as part of the current work. The trends in the phytochemistry, pharmacological mechanisms and activities of Ficus genus are overviewed in this manuscript: antimicrobial, antidiabetic, anti-inflammatory and analgesic activity, antiseizure and anti-Parkinson's diseases, cytotoxic and antioxidant. Health-promoting effects, recent human clinical studies, safety and adverse effects of Ficus plants also are covered. The medical potential and long-term pharmacotherapeutic use of the genus Ficus along with no serious reported adverse events, suggests that it can be considered as being safe.

Multivesicular Liposome (Depofoam) in Human Diseases.

Drug development is a key point in the research of new therapeutic treatments for increasing maximum drug loading and prolonged drug effect. Encapsulation of drugs into multivesicular liposomes (DepoFoam) is a nanotechnology that allow delivery of the active constituent at a sufficient concentration during the entire treatment period. This guarantees the reduction of drug administration frequency, a very important factor in a prolonged treatment. Currently, diverse DepoFoam drugs are approved for clinical use against neurological diseases and for post-surgical pain management while other are under development for reducing surgical bleeding and for post-surgical analgesia. Also, on pre-clinical trials on cancer DepoFoam can improve bioavailability and stability of the drug molecules minimizing side effects by site-specific targeted delivery. In the current work, available literature on structure, preparation and pharmacokinetics of DepoFoam are reviewed. Moreover, we investigated approved DepoFoam formulations and preclinical studies with this nanotechnology.

Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases.

Oxidative stress plays an essential role in the pathogenesis of chronic diseases such as cardiovascular diseases, diabetes, neurodegenerative diseases, and cancer. Long term exposure to increased levels of pro-oxidant factors can cause structural defects at a mitochondrial DNA level, as well as functional alteration of several enzymes and cellular structures leading to aberrations in gene expression. The modern lifestyle associated with processed food, exposure to a wide range of chemicals and lack of exercise plays an important role in oxidative stress induction. However, the use of medicinal plants with antioxidant properties has been exploited for their ability to treat or prevent several human pathologies in which oxidative stress seems to be one of the causes. In this review we discuss the diseases in which oxidative stress is one of the triggers and the plant-derived antioxidant compounds with their mechanisms of antioxidant defenses that can help in the prevention of these diseases. Finally, both the beneficial and detrimental effects of antioxidant molecules that are used to reduce oxidative stress in several human conditions are discussed.

Fruits of Terminalia chebula Retz.: A review on traditional uses, bioactive chemical constituents and pharmacological activities.

Fruits of Terminalia chebula Retz. (Combretaceae) are widely used as crude drugs in various traditional medicine systems. The aim of this article is to review the available scientific information regarding the traditional uses, bioactive chemical constituents and the pharmacological activities of T. chebula. Numerous researches conducted on T. chebula have confirmed the presence of wide range of the phytochemicals such as flavonoids, tannins, phenolic acids and other bioactive compounds. T. chebula is also widely studied regarding its pharmacological activities such as antioxidant, hepatoprotective, neuroprotective, cytotoxic, antidiabetic, anti-inflammatory activities among others. However, more in vivo and clinical studies for mechanism-based pharmacological evaluation should be conducted in future to provide stronger scientific evidences for their traditional uses.

Areca catechu-From farm to food and biomedical applications.

The family Arecaceae includes 181 genera and 2,600 species with a high diversity in physical characteristics. Areca plants, commonly palms, which are able to grow in nearly every type of habitat, prefer tropical and subtropical climates. The most studied species Areca catechu L. contains phytochemicals as phenolics and alkaloids with biological properties. The phenolics are mainly distributed in roots followed by fresh unripe fruits, leaves, spikes, and veins, while the contents of alkaloids are in the order of roots, fresh unripe fruits, spikes, leaves, and veins. This species has been reputed to provide health effects on the cardiovascular, respiratory, nervous, metabolic, gastrointestinal, and reproductive systems. However, in many developing countries, quid from this species has been associated with side effects, which include the destruction of the teeth, impairment of oral hygiene, bronchial asthma, or oral cancer. Despite these side effects, which are also mentioned in this work, the present review collects the main results of biological properties of the phytochemicals in A. catechu. This study emphasizes the in vitro and in vivo antioxidant, antimicrobial, anticancer, and clinical effectiveness in humans. In this sense, A. catechu have demonstrated effectiveness in several reports through in vitro and in vivo experiments on disorders such as antimicrobial, antioxidant, or anticancer. Moreover, our findings demonstrate that this species presents clinical effectiveness on neurological disorders. Hence, A. catechu extracts could be used as a bioactive ingredient for functional food, nutraceuticals, or cosmeceuticals. However, further studies, especially extensive and comprehensive clinical trials, are recommended for the use of Areca in the treatment of diseases.

Targeting Glycoproteins as a therapeutic strategy for diabetes mellitus and its complications.

OBJECTIVES: Glycoproteins are organic compounds formed from proteins and carbohydrates, which are found in many parts of the living systems including the cell membranes. Furthermore, impaired metabolism of glycoprotein components plays the main role in the pathogenesis of diabetes mellitus. The aim of this study is to investigate the influence of glycoprotein levels in the treatment of diabetes mellitus. METHODS: All relevant papers in the English language were compiled by searching electronic databases, including Scopus, PubMed and Cochrane library. The keywords of glycoprotein, diabetes mellitus, glycan, glycosylation, and inhibitor were searched until January 2019. RESULTS: Glycoproteins are pivotal elements in the regulation of cell proliferation, growth, maturation and signaling pathways. Moreover, they are involved in drug binding, drug transportation, efflux of chemicals and stability of therapeutic proteins. These functions, structure, composition, linkages, biosynthesis, significance and biological effects are discussed as related to their use as a therapeutic strategy for the treatment of diabetes mellitus and its complications. CONCLUSIONS: The findings revealed several chemical and natural compounds have significant beneficial effects on glycoprotein metabolism. The comprehension of glycoprotein structure and functions are very essential and inevitable to enhance the knowledge of glycoengineering for glycoprotein-based therapeutics as may be required for the treatment of diabetes mellitus and its associated complications. Graphical abstract.

Phytosterols: From Preclinical Evidence to Potential Clinical Applications.

Phytosterols (PSs) are plant-originated steroids. Over 250 PSs have been isolated, and each plant species contains a characteristic phytosterol composition. A wide number of studies have reported remarkable pharmacological effects of PSs, acting as chemopreventive, anti-inflammatory, antioxidant, antidiabetic, and antiatherosclerotic agents. However, PS bioavailability is a key issue, as it can be influenced by several factors (type, source, processing, preparation, delivery method, food matrix, dose, time of administration into the body, and genetic factors), and the existence of a close relationship between their chemical structures (e.g., saturation degree and side-chain length) and low absorption rates has been stated. In this sense, the present review intends to provide in-depth data on PS therapeutic potential for human health, also emphasizing their preclinical effects and bioavailability-related issues.

Cordyceps spp.: A Review on Its Immune-Stimulatory and Other Biological Potentials.

In recent decades, interest in the Cordyceps genus has amplified due to its immunostimulatory potential. Cordyceps species, its extracts, and bioactive constituents have been related with cytokine production such as interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor (TNF)-α, phagocytosis stimulation of immune cells, nitric oxide production by increasing inducible nitric oxide synthase activity, and stimulation of inflammatory response via mitogen-activated protein kinase pathway. Other pharmacological activities like antioxidant, anti-cancer, antihyperlipidemic, anti-diabetic, anti-fatigue, anti-aging, hypocholesterolemic, hypotensive, vasorelaxation, anti-depressant, aphrodisiac, and kidney protection, has been reported in pre-clinical studies. These biological activities are correlated with the bioactive compounds present in Cordyceps including nucleosides, sterols, flavonoids, cyclic peptides, phenolic, bioxanthracenes, polyketides, and alkaloids, being the cyclic peptides compounds the most studied. An organized review of the existing literature was executed by surveying several databanks like PubMed, Scopus, etc. using keywords like Cordyceps, cordycepin, immune system, immunostimulation, immunomodulatory, pharmacology, anti-cancer, anti-viral, clinical trials, ethnomedicine, pharmacology, phytochemical analysis, and different species names. This review collects and analyzes state-of-the-art about the properties of Cordyceps species along with ethnopharmacological properties, application in food, chemical compounds, extraction of bioactive compounds, and various pharmacological properties with a special focus on the stimulatory properties of immunity.