Cardioprotective Role of Tinospora cordifolia against Trimethylamine-NOxide and Glucose Induced Stress in Rat Cardiomyocytes.

BACKGROUND: Type 2 diabetes has become a concern issue that affects the quality of life and can increase the risk of cardiac insufficiency elevating the threat to the life safety of patients. A recognized cause of cardiac insufficiency is diabetic cardiomyopathy, chronic hyperglycemia, and myocardial lipotoxicity which can reduce the myocardial contractile performance, and enhance the cardiomyocyte hypertrophy and interstitial fibrosis. The cause of diabetic cardiomyopathy is multi-factorial which includes oxidative stress, insulin resistance, inflammation, apoptosis, and autophagy. Recent clinical studies have suggested the dysbiosis of gut microbiota, secretion of metabolites, and their diffusion in to the host as to have direct detrimental effects on the cardiac contractility. MATERIAL AND METHODS: In the present paper, we have done in silico studies including molecular interaction of phytoconstituents of Tinospora cordifolia against reactive oxygen species producing proteins. Whereas, in vitro studies were conducted on H9C2 cardiac cells including cell morphological examination, level of reactive oxygen species, cell count-viability, apoptotic status, in the presence of high glucose, trimethylamine-n-oxide, and plant extracts which were determined through cell analyzer and microscopic assays. RESULTS: The treatment of high glucose and trimethylamine-n-oxide was found to be increase the cardiac stress approximately two fold by attenuating hypertrophic conditions, oxidative stress, and apoptosis in rat cardiomyocytes, and Tinospora cordifolia was found to be a cardioprotective agent. CONCLUSION: Conclusively, our study has reported that the Indian medicinal plant Tinospora cordifolia has the ability to treat diabetic cardiomyopathy. Our study can open up a new herbal therapeutic strategy against diabetic cardiomyopathy.

Therapeutic Potential of Syzygium aromaticum in Gut Dysbiosis via TMAO Associated Diabetic Cardiomyopathy.

BACKGROUND: Dysbiosis of the gastrointestinal microbiota is not only related to the pathogenesis of intestinal disorders but also associated with extra-intestinal diseases. Various studies have revealed the role of an imbalance of intestinal microbiota and their metabolites including bile acids, indole derivatives, polyamines, and trimethylamine in the progression of various diseases. The elevated plasma level of the oxidized form of trimethylamine is associated with an increased risk of cardiovascular diseases. Literature supports that herbal medicines can modulate human health by altering the diversity of gut microbiota and their metabolites and proposes the use of prebiotics to improve dysbiotic conditions as a new way of therapeutic strategy. MATERIAL AND METHODS: In silico studies including drug likeliness, toxicity prediction, and molecular interaction of phytochemicals against trimethylamine lyase enzyme have been done. Antimicrobial activity of extracts of selected plant i.e. Syzygium aromaticum was done by disc diffusion and the protective effects of plant compounds were examined on trimethylamine-n-oxide a bacterial metabolic product induced toxicity on cardiac cells. RESULTS: The current study has found that the phytochemicals of S. aromaticum identified as nontoxic and followed the standard rules of drug likeliness and showed a significant binding affinity against trimethylamine-n-oxide producing enzymes. Furthermore, S. aromaticum extract was found to have antimicrobial potential and cardioprotective effects by reducing the production of intracellular reactive oxygen species and correcting the distorted nuclear morphology in the presence of high trimethylamine-n-oxide. CONCLUSION: Conclusively, our study explored the herbal intervention in intestinal dysbiosis and suggested a natural therapy against dysbiosis associated with cardiac disease, and S, aromaticum was found to have exceptional cardioprotective potential against TMAO induced gut dysbiosis, which provides a novel future therapeutic intervention for treating cardiovascular complications.

Role of gut microbiota in tumorigenesis and antitumoral therapies: an updated review.

Gut microbiota plays a prominent role in regulation of host nutrientmetabolism, drug and xenobiotics metabolism, immunomodulation and defense against pathogens. It synthesizes numerous metabolites thatmaintain the homeostasis of host. Any disbalance in the normalmicrobiota of gut can lead to pathological conditions includinginflammation and tumorigenesis. In the past few decades, theimportance of gut microbiota and its implication in various diseases, including cancer has been a prime focus in the field of research. Itplays a dual role in tumorigenesis, where it can accelerate as wellas inhibit the process. Various evidences validate the effects of gutmicrobiota in development and progression of malignancies, wheremanipulation of gut microbiota by probiotics, prebiotics, dietarymodifications and faecal microbiota transfer play a significant role.In this review, we focus on the current understanding of theinterrelationship between gut microbiota, immune system and cancer,the mechanisms by which they play dual role in promotion andinhibition of tumorigenesis. We have also discussed the role ofcertain bacteria with probiotic characteristics which can be used tomodulate the outcome of the various anti-cancer therapies under theinfluence of the alteration in the composition of gut microbiota.Future research primarily focusing on the microbiota as a communitywhich affect and modulate the treatment for cancer would benoteworthy in the field of oncology. This necessitates acomprehensive knowledge of the roles of individual as well asconsortium of microbiota in relation to physiology and response ofthe host.

Therapeutic Effects of Gut Microbiota on Metabolic Syndrome: A Patent Review.

BACKGROUND: The balanced composition of the gut microbiota is essential for human health. The dysbiotic condition may develop various complex diseases. A metabolic syndrome is a group of biochemical and physiological abnormalities that can increase the risk of cardiovascular diseases, diabetes, and inflammatory diseases. It has become a serious concern worldwide because there is no acceptable medication to overcome this problem. OBJECTIVE: This review aims to evaluate the relationship between gut microbiota and metabolic syndrome. The balance of gut microbiota relates to human health as well as diseases. Patents related to significant findings on probiotics, prebiotics, synbiotics, and fecal microbiota transplantation signify the importance of the proposed theme and provide promising therapeutic strategies to modulate the dysbiotic condition and reoccurrence of beneficial microbial species during metabolic syndromes. Screening of patents-related databases can be worth full to track new technology. Therefore, some selected recent patents related to gut microbiota and associated therapies have been discussed in the present manuscript. CONCLUSION: Under the existing situation, the role of gastrointestinal microbiota as a therapeutic agent is becoming more utilized for treating human health issues and various metabolic syndromes including obesity, diabetes, and cardiovascular diseases. Understanding gut dysbiosis and associated complex interactions between microbes and hosts would be effective for designing future therapeutic interventions for metabolic syndrome. Our detailed patent analysis reflects that gut dysbiosis has a prominent role in metabolic syndromes and dietary therapeutic strategies can improve health by modulating the human microbiota, their metabolites ad stability.

A Rare Case of Giant-Cell Tumor of Hand in a Young Male.

Giant-cell tumor (GCT) of the bone affecting the hand is a rare lesion that is usually diagnosed at an advanced stage and has a high rate of recurrence. In the current literature, GCT is described as a predominantly osteoclastogenic stromal cell tumor of mesenchymal origin. It is composed of three cell types: the neoplastic GCT stromal cells; mononuclear monocyte cells; and multinucleated giant cells. Clinical imaging is basic for the diagnosis of a GCT. This tumor within the hand tends to be less eccentric and most often central. GCT of metacarpals is noted to be a rare location, with the incidence being as low as 2%. GCT on hand as compared to other sites is locally more aggressive, grows faster, and has a higher recurrence rate. A 22-year-old male patient presented with swelling over the left hand for 7 months, spontaneous in onset, gradually progressive in size, and painfully restricting the joint movement, with no history of fall or trauma. On examination, diffuse swelling of size 5 × 5 × 3 cm was tender on palpation, restricting the movement at the 4th metacarpophalangeal joint. A plain radiograph followed by an MRI scan revealed a Campanacci's Grade III GCT of the 4th metacarpal. An open biopsy showed an expanded and lytic mass with areas of hemorrhage and necrosis. There were few mitotic figures and the tumor was diagnosed to be a GCT. On surgical resection, friable tumor tissue was noted over the region of the entire 4th metacarpal except for the base. The patient was managed by surgical intralesional excision of the mass, followed by Kirschner-wire fixation and reconstruction with synthetic bone graft. The excised tissue was sent for histopathological examination. The patient was followed up at regular intervals, with initial splinting, followed by wire removal at 6-week post-op, and with adequate physiotherapy, as tolerated by the patient. On a 3-month follow-up, the range of motion had returned to a functional level, with good uptake of graft, and no other complications. GCT of the hand is a rare presentation of the disease and requires meticulous workup, including a thorough clinical exam, hematological, radiological, and pathological workup. The various treatment modalities described in the literature for GCTs are curettage alone, curettage and bone graft, en-bloc resection, amputation, and resection with reconstruction, but curettage alone or curettage with bone graft is not effective even for GCTs of long bones and hand, too. Such a procedure creates a skeletal void and hence furthers the need for a challenging reconstructive procedure requiring reconstruction using autograft, allograft, or silastic (synthetic) implant.

Study to Explore Plant-Derived Trimethylamine Lyase Enzyme Inhibitors to Address Gut Dysbiosis.

Lifestyle complications are major health concerns around the globe and are recognized as a major factor for the development of various chronic diseases such as obesity, diabetes, inflammatory bowel diseases, cancer, and cardiac diseases. An unhealthy diet and poor lifestyle impose a serious threat to human health. Numerous studies have suggested the role of human microbiota in human health and diseases. Microbiota resides in the human body symbiotically and the composition of microorganisms is crucial for maintaining the healthy state of an individual. A dysbiotic gut microbiome is responsible for the release of toxic metabolites such as trimethylamine, lipopolysaccharides, bile acids, and uremic toxins and is associated with impaired organ functions. Dietary and herbal intervention of dysbiosis proposes a promising strategy to counteract gut alterations and repairing of the microbial ecosystem and health. The objective of the present comparative study was to observe the effect of therapeutic herbs in gut dysbiosis. In silico studies were performed to identify human microbiota associated with various diseases, ADME, and toxicity properties of phytoconstituents of "Tinospora cordifolia" and "Ocimum sanctum." Furthermore, co-interaction studies were performed to observe the affinity of selected phytochemicals against choline trimethylamine lyase, a critical enzyme involved in dysbiosis-induced human diseases. The antimicrobial potential of phytocompounds was done by the disc diffusion method. In conclusion, our work discusses the herbal intervention of gut dysbiosis and proposes a natural, safe, and effective herbal formulation to correct microbial dysbiosis and associated diseases.

Human Gut Microbiome: A New Frontier in Cancer Diagnostics & Therapeutics.

The field of oncology is vast and ever-growing. The present cancer therapeutics is continually exhibiting various drawbacks, which opens the door for exploring better novel therapeutic techniques. One such emerging technique is the manipulation of gut microbiota to induce a positive curative effect in the body. The dynamic gut microbiota of our body houses an astonishing number of microorganisms, mainly bacteria. The balance of the gut microbiota is essential for good health as imbalances may result in dysbiosis leading to various diseases such as cancer. The gut microbiota can be manipulated by using prebiotics, probiotics, synbiotics, postbiotics, and antibiotics for better therapeutic outcomes, as well as to improve the quality of life of patients undergoing conventional cancer treatment. Administration of bacteria as a probiotic agent accompanied with prebiotics obtained from a wide variety of herbs has been used effectively to enhance the treatment of various cancers. Although the theoretical basis of Gut therapy can be ascertained, further clinical trials will be essential to determine the scope and limitations fully. The present review provides a glimpse of conventional and novel cancer therapeutics and their drawbacks, along with the role of the gut microbiome and its modulation to design new pharmaceutics against cancer.

--Immunophenotypic Aberrancies in Acute Leukemia: A Tertiary Care Centre Experience.

OBJECTIVES: Acute leukemias (AL) are a heterogeneous group of hematological malignancies with the presence of 20% or more blasts in the peripheral blood or bone marrow. Malignant cells display characteristic patterns of surface antigenic expression. Aberrant phenotypes are defined as patterns of antigen expression on neoplastic cells different from the process of normal hematopoietic maturation. We sought to evaluate the occurrence of aberrant phenotypes in newly diagnosed cases of AL. METHODS: The study included 100 patients in whom both bone marrow aspiration and flow cytometry were performed. Patients with blasts > 20% of all ages were included in the study. Flow cytometric analysis was done using the monoclonal antibody panel of peripheral blood/bone marrow. RESULTS: Out of 100 cases, 53 were categorized as acute myeloid leukemia (AML), 43 as acute lymphoid leukemia (ALL), and four cases of mixed phenotypic acute leukemia (MPAL). ALL were subcategorized based on immunophenotyping into B-ALL and T-ALL, which comprised 88.4% and 11.6%, respectively, of total ALL (43.0%) cases. Cluster of differentiation 33 (CD33) and CD13 were the most commonly expressed antigens in AML, with CD7 being the most common aberrancy. CD19 was expressed in all B-ALL cases followed by cCD79a, CD10, Tdt (86.8%) with CD13 being the most common aberrancy. cCD3, CD7, and CD5 were expressed in all T-ALL cases with aberrant antigen expression in 80.0% of T-ALL cases. MPAL cases showed expression of B/myeloid antigens. CONCLUSIONS: The diagnosis and classification of leukemia rely on the simultaneous application of cytomorphology, cytochemistry, flow cytometry, cytogenetics, and molecular techniques. Flow cytometry is of great help in the diagnosis of AL, particularly in ALL for lineage assignment and in classifying MPAL. It also helps in detecting aberrant antigen expression and assisting in minimal residual disease detection.