New and potential therapies for the treatment of Breast Cnacer An update for oncologists

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Dr Varruchi Sharma

Breast Cancer

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New and potential therapies for the treatment of Breast Cnacer An update for oncologists

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Vaccines are proved to be boon for the prevention of infectious diseases and provide acquired immunity against life threatening infections. The lethality of infectious diseases has decreased due to vaccination as it is one of the safe and effective measure to control various infectious diseases. A protein which acts as the vaccine, present in food and consumed as the internal composition of food is known as the edible vaccine. As the name suggests, the term “Edible vaccines” was first used by Charles Arntzen in 1990 and refers to plants that produce vitamins, proteins or other nourishment that act as a vaccine against a certain disease. These vaccines are capable to stimulate the body’s immune system to recognize the antigen. Edible vaccines have been the newer form of vaccines which have the power to cover the risks associated with conventional vaccines. The main mechanism of action of edible vaccines is to activate the systemic and mucosal immunity responses against a foreign disease-causing organism. Edible vaccines are produced by the incorporation of the selected desired genes into the plants and then modified to produce the encoded proteins, providing immunity for certain diseases. Identification, isolation and characterization of a pathogenic antigen is important for making an edible vaccine. At present edible vaccine are developed for various veterinary and human diseases such as cholera, measles, hepatitis and foot and mouth diseases. Current review highlights the importance of edible vaccines which could prove to be cost effective, efficient and safe and would not require refrigeration, making them more accessible to poor people as compared to traditional vaccines.

PROBING INTO THE EDIBLE VACCINES: NEWER PARADIGMS, SCOPE AND RELEVANCE

Dr Varruchi Sharma

One of the largest families of membrane proteins, the G protein-coupled receptors (GPCRs) has been a very important target of drug discovery as they are involved in having a regulatory role in a variety of signaling pathways at the cellular level in response to external stimuli. Modern in-silico and crystallographic approaches have further made it easier to peep into their structures. In this study, β2 adrenergic receptor (β2AR) has been targeted, and a new ligand molecule using the de-novo approach has been proposed. Using 1-Amino-3-(2,3-dihydro-1H-indol-4-yloxy)-propan-2-ol, the best fitting binding fragments were established with a significant dissociation constant value of 5-7 nanomolar. The flexibility of specific active sites was also investigated, and it was observed that residues 114 (V), 117 (V), 203 (S), 286 (W), and 289 (F) played a crucial role in accommodating ligand for the best binding. Upon examination of the bioavailability parameters, the ligand var9 exhibited significant inhibitory characteristics having lower toxicity values and high drug likeliness properties. Findings certainly hold significance in terms of targeting GPCRs in getting insight into structure-based drug designing and drug discovery.

An In-Silico Approach for Designing a Potential Antagonistic Molecule Targeti...

Dr Varruchi Sharma

Oral squamous cell carcinoma (OSCC) has been considered to be the most common malignancy of the head and neck region. OSCC develops as a result of certain genetic and epigenetic variations in the squamous epithelium, which in turn leads to a series of consequences leading to the definitive stage of invasive squamous cell carcinoma. Majority of oral malignancy cases have been associated with specific exposure to certain risk factors such as smoking, smokeless tobacco products, heavy consumption of alcohol, poor oral hygiene, human papilloma virus infection along with other lifestyle factors and dietary changes. There are certain genes named as BIRC2 and BIRC3 belonging to the inhibitors of apoptosis protein (IAP) family which become over-expressed and upregulated during the course of OSCC. The proteins made are pronounced as cIAPs which are inhibitors of specific caspases leading to the suppression of apoptosis induced by a variety of triggering factors. Current review has brought together all such concrete studies along with diagnostic and therapeutic relevance to OSCC at a single platform so as to understand the etiological factors, mechanism and regulation in oral squamous cell carcinoma. Moreover, the recent emergence of microbiome as a diagnostic and therapeutic target has also been discussed in order to find a sustainable and reliable therapeutic solution to OSCC.

Oral squamous cell carcinoma (OSCC) in humans: Etiological Factors, diagnosti...

Dr Varruchi Sharma

The levels of protein tyrosine phosphorylation within a cell is regulated by protein tyrosine kinases and protein tyrosine phosphatases. These protein tyrosine phosphatases (PTP) can act both as positive and negative regulators during cell cycle progression and signal transduction. Phosphatase activity is shown by Phosphatase and Tensin homolog (PTEN) protein encoded by PTEN gene localized on human chromosome 10. Earlier findings established the role of PTEN as a tumor suppressor in Cowden’s disease, where PTEN mutations resulted in disease outcomes. Subsequent studies found the role of PTEN mutations in various human cancers, making it one of the vastly studied tumor suppressor genes. The current review has been planned to get a deeper insight into the potential role of PTEN in a variety of physiological processes involved in normal development like cell growth, migration, and differentiation along with the factors, regulation, and underlying mechanism

Essence of PTEN: a Broad-Spectrum Therapeutic Target in Cancer

Dr Varruchi Sharma

It has been suggested that an intricate communication link exists between the gut microbiota and the brain and its ability to modulate behaviour of an individual governing homeostasis. Metabolic activity of the microbiota is considered to be relatively constant in healthy individuals, despite diff erences in the composition of microbiota. The metabolites produced by gut microbiota and their homeostatic balance is often perturbed as a result of neurological complications. Therefore, it is of paramount importance to explore the link between gut microbiota and brain function and behaviour through neural, endocrine, and immune pathways. This current review focusses on the impact of altered gut microbiota on brain functions and how microbiome modulation by use of probiotics, prebiotics, and synbiotics might prove benefi cial in the prevention and/or treatment of neurological disorders. It is important to carefully understand the complex mechanisms underlying the gut–brain axis so as to use the gut microbiota as a therapeutic intervention strategy for neurological disorders.

Current Paradigms to Explore the Gut Microbiota Linkage to Neurological Disor...

Dr Varruchi Sharma

Recent pandemic of corona virus disease caused by a novel coronavirus SARS-CoV-2 in humans is the third outbreak by this family of viruses, which is reminiscent of the SARS-COV outbreak happened in the year 2003. General characteristics of the novel coronavirus (SARS-CoV-2) especially in regards to the disease susceptibility amongst males and females have been focused providing a better understanding of the coronavirus disease (COVID-19) in males, females and children. A thorough literature search for articles in major databases such as PubMed and Google Scholar etc. has been carried out. COVID-19 has been known to have varied symptoms ranging from mild flu-like symptoms to acute respiratory distress syndrome, multiple organ failure and death. Ageing, genetics, comorbidities and many other associated factors may play a crucial role in predisposing an individual towards COVID-19 disease as there exists chronic inflammation, thrombosis and immune response impairment due to SARS-CoV-2 providing a therapeutic window. Current study emphasizes upon the role of gender in morbidity and mortality in patients with COVID-19 with men higher at risk to COVID-19 than women in terms of mortality despite having the similar prevalence of the disease. The study has been well supported by the data available from the hot-spots affected states from Indian subcontinent. However, current evidence is not sufficient to conclude on the gender-bias susceptibility but certainly men have an edge over women in terms of susceptibility towards COVID-19.

GENDER-BIAS SUSCEPTIBILITY OF CORONA VIRUS DISEASE : PEEPING INTO THE FACTORS...

Dr Varruchi Sharma

The world population is aging, and cancer is always considered to be one of the major causes of death all over the globe. The advent of recent drug-targeted therapies undoubtedly is going to reduce the incidence of cancer over the coming years. However, the frequency of occurrence of such chronic diseases like cancer would continue to increase. Therefore, the search for a safer and cost-effective treatment is urgently needed. Phytochemicals found in plants, foods, vegetables, tea, etc. have emerged as proven therapeutic compounds modulating signaling pathways involved in cancer. We carried out a structured search of bibliographic databases for peer-reviewed research literature using the keywords: cancer chemoprevention, flavonoids, dietary polyphenols, terpenoids, bioactive, microbiota. Quality of the retrieved papers and characteristic outcomes of the articles included in the study was assessed by employing standard tools and deductive qualitative content analysis methodology. The development of personalized supplements comprising particular phytochemicals has been the key, especially dealing with chronic inflammatory disorders like cancer. Better understanding at the molecular level explains the influence of phytochemicals on human health, which has been extensively covered through this review. Moreover, the wide collection of dietary polyphenols that has significant properties in reference to human health has been highlighted. Furthermore, the etiology of end products of such phytochemicals, especially on the modulation of gut microbiota and the host-microbial interactions thereof, need to be properly understood. The present study summarizes the chemoprevention and treatment of cancer using the bioactive components, including flavonoids, dietary polyphenols, and terpenoids. Likewise, the effect of dietary polyphenols on the human gut microbiota has been realized more recently. However, more research is needed in this field, especially focused on the communications, interlinks between the gut microbiota and polyphenols with the precise mechanism of action.

Cancer Chemoprevention by Flavonoids, Dietary Polyphenols and Terpenoids

Dr Varruchi Sharma

Being an aquatic weed which is growing dense and widespread across many lakes and water bodies, it is of paramount importance to utilize Eichhornia crassipes (commonly known as water hyacinth) for the benefit of the mankind, especially for its value added and medical properties, such as bio-fuel, biogas, bioremediation and therapeutics. Many of the bird sanctuaries and water-bodies have been drastically invaded by this aquatic weed which is really affecting ecological niche and bird migrations. Several researchers have successfully demonstrated the use of water hyacinth in the bio-remediation and as a potential source of renewable energy. Different heavy and toxic metals showing biomagnifications and therefore creating health hazards, could be remediated by using water hyacinth. The process of decontaminating agro-industrial waste polluted with heavy metals, organic and inorganic pollutants could possibly be done using water hyacinth. Current review focuses towards the efforts to utilize this weed for different value added and therapeutic properties. Furthermore the article emphasizes upon the need to gain more insight into the mechanism with concrete randomized controlled studies to find out the effects of this weed on human health and a sustainable solution to exploit and manage this invasive otherwise harmful weed into a beneficial entity for the mankind.

MULTIFACETED POTENTIAL OF EICHHORNIA CRASSIPES (WATER HYACINTH) LADENED WITH ...

Dr Varruchi Sharma

Disease can occur due to alterations in many physiological processes. A variety of factorsare known to be involved in the progression of cancer, a chronic diseasethat occurs due to permissible proliferative signaling, avoiding growth suppressors, resisting cell death, allowing replicative immortality, induction of angiogenesis, and inducing invasion and metastasis, along with reprogramming of metabolic pathways involved in energy production and avoiding the host immune response for cell destruction. Treatment of such a multifactorial disease has very less cure rate because of the singular agents tried in the past for targeting. Molecular level studies with deeper insight are urgently neededthat focus on the most promising herbal-derived bioactive substances for which thorough research was carried out in the literature in various data-bases such as PUB-MED, MEDLINE, SCOPUS indexed journals etc. to look for systematic reviews of the protocols or data interpretation, natural drug/immunological properties and validation. As immune system plays avery important role in the proliferation or suppression of cancer and other autoimmune diseases, It is the dire need to study the effect of such natural compound on the immune system so that a possible drug target or epitope can be identified for the treatment of such diseases. In nutshell there are many nonclinical in vitro and in vivo studies on herbal medicines which commonly supports the traditional therapeutic claims. It has been seen from the previos studies in literature that the yield and composition of bioactive compounds derived from plants are dependent upon the production source,culturing conditions and extraction protocols.Therefore appropriate optimization conditions would certainly assist the medical and scientific fraternity to accept herbal products as potential candidates for cancer treatment. In this article we explored the different natural products, their immunological effects concerning cancer with no or negligible side effects. However,one has to look for potential herb–drug or herb-epitope interactions and how immune system responds to such drugs.

Anti cancer potential of natural products..pdf

Dr Varruchi Sharma

Malaria is a global problem affecting a large population without any demarcation between developed and developing world communities. The already approved compounds for the treatment of the disease hold significant efficacy but the emergence of resistant strains and reduced efficacy of drugs against the disease leave the scope for the identification of noval natural products as potential therapeutic agents. There are seven major classes of antiplasmodium agents which are plant secondary metabolites and can be used as a potential antimalarial drugs. In the present review, the focus is on the antimalarial compounds which have been isolated from plants which could be potentially used as antimalarial drugs.

Role of plant secondary metabolites as potential antimalarial drugs

Dr Varruchi Sharma

Severe acute respiratory syndrome coronavirus -2 (S ARS-CoV-2) emerging variants particularly those of concern contain numerous mutations that influence the behavior and transmissibility of the virus and could adversely affect the efficacies of existing coronavirus disease 2019 (COVID-19) vaccines and immunotherapies. The emerging SARS-CoV-2 variants have resulted in different waves of the pandemic within the ongoing COVID-19 pandemic. On 26 November 2021 World Health Organization designated omicron (B.1.1.529) as the fifth variant of concern which was first reported from South Africa on November 24, 2021, and thereafter rapidly spread across the globe owing to its very high transmission rates along with impeding efficacies of existing vaccines and immunotherapies. Omicron contains more than 50 mutations with many mutations (26-32) in spike protein that might be associated with high transmissibility. Natural compounds particularly phytochemicals have been used since ancient times for the treatment of different diseases, and owing to their potent anti-viral properties have also been explored recently against COVID-19. In the present study, molecular docking of nine phytochemicals (Oleocanthal, Tangeritin, Coumarin, Malvidin, Glycitein, Piceatannol, Pinosylnin, Daidzein, and Naringenin) with omicron spike protein (7QNW (electron microscopy, resolution 2.40 Å) was done. The docking study revealed that selected ligands interact with the receptor with binding energy in the range of -6.2 to-7.0 kcal/mol. Pinosylnin showed the highest binding energy of -7.0 kcal/mol which may be used as potential ligands against omicron spike protein. Based on the docking studies, it was suggested that these phytochemicals are potential molecules to be tested against omicron SARS-CoV-2 and can be used to develop effective antiviral drugs.

Targeting Omicron (B.1.1.529) SARS CoV-2 spike protein with selected phytoche...

Dr Varruchi Sharma

Monkeypox is a zoonotic viral infection caused by monkeypox virus which belongs to the Poxviridae family of genus Orthopoxvirus. Usually the virus transmission happens when the individual comes in contact with the infected person through body fluids, animal lesions, respiratory droplets or through virus contaminated materials. Clinical presentation of the monkeypox has shown significant resemblance to that of smallpox and chickenpox, belonging to the same orthopoxvirus genus but were eradicated during 1980s globally. Monkeypox may lead to a range of medical complications including clinical symptoms like fever, rashes, headaches, back pain, myodynia and swollen lymph nodes. As far as the treatment modalities are concerned,the antiviral therapeutic agents developed for the smallpox treatment, were also permitted to be used for the monkeypox treatment. However, there is no proven treatment for human monkeypox. in the current study, we have focused on designing of a best probable ligand against the target MPXVgp158 (Monkeypox virus protein). Since tecovirimat is an FDA approved compound known as an antipoxviral drug, the study aimed to develop a Monkeypox virus protein MPXVgp158 inhibitor which is bioavailable and biocompatible as well through drug designing using computational tools. Molecular docking (MD) analysis displayed tecovirimat with lesser binding energy, higher non-bonded interaction capability, and more stability against MPXVgp158, with efficient binding mode of interactions. Hence, tecovirimat was adjudged to be the potential candidate against MPXVgp158 inhibition.

tecovirimat as a Potential Bioavailable inhibitor against MPXVgp158 establish...

Dr Varruchi Sharma

Monkeypox virus is an orthopoxvirus sharing the common genus with variola and vaccinia virus. Most of the monkeypox (MPX) cases had been reported from the central and west African region (the main endemic areas) prior to 2022 but there was a sudden outbreak in May, 2022 disseminating the infections to thousands of people even in non-endemic countries, posing a global public health emergency. MPX was considered a rae and neglected disease, however the 2022 MPX outbreaks in multiple countries attracted attention of worldwide researchers to pace up for carrying out researches on various aspects of MPXV including attempts to design and develop diagnostics, vaccines, drugs and therapeutics counteract MPX. Apart from being a zoonotic disease, the current outbreaks highlighted rapid human-to-human transmission of MPXV, besides the reverse zoonosis has also been documented with recent first report of human-to-dog transmission, urging a call for the importance of one health approach. Atypical and unusual disease manifestations as well asymptomatic MPXV infections have also been observed during 2022 MPX outbreak. the affected patients typically develop a rash resulting in a mild disease followed by recovery with some supportive care and use of antivirals such as tecovirimat, cidofovir and brincidofovir in severe disease cases. Modified vaccinia Ankara (MVA) vaccine with an excellent safety profile has been recommended to patients with higher risk exposure and immunocompromised individuals. Moreover, another vaccine the replication-competent vaccine (ACAM2000) could be a suitable alternative to MVA’s non-availability to some selective immunocompetent individuals. Current review highlights the salient aspects of management and treatment of monkeypox along with underlying promises in terms of therapeutics and a variety of challenges posed due to current global public health emergency situation to counteract MPX.

An overview on Monkeypox, Current Paradigms and Advances in its Vaccination, ...

Dr Varruchi Sharma

The most recurrent cause of cancer-related deaths worldwide in women is the breast cancer. The key to diagnosis is early prediction and a curable stage but still treatment remains a great clinical challenge. Origin of the Problem: A number of studies have been carried out for the treatment of breast cancer which includes the targeted therapies and increased survival rates in women. Essential PI3K/mTOR signaling pathway activation has been observed in most breast cancers. The cell growth and tumor development in such cases involves phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) complex intracellular pathway. Hypothesis: Through preclinical and clinical trials, it has been observed that there are a number of other inhibitors of PI3K/Akt/mTOR pathway, which either alone or in combination with cytotoxic agents can be used for endocrine therapies. Conclusions: Structure and regulation/deregulation of mTOR provides a greater insight into the action mechanism. Also through this review, one could easily scan first and second generation inhibitors for PI3K/Akt/mTOR pathway besides targeted therapies for breast cancer and the precise role of mTOR.

PI3KAktmTOR Intracellular Pathway and Breast Cancer Factors, Mechanism and Re...

Dr Varruchi Sharma

Worldwide breast cancer causes significant fatalities in women. The effective therapeutic solution for treating the disease is using new and probable antagonistic biologically available ligands as anticancer drugs. To identify a successful therapeutic approach, the scientific community is now interested in creating novel ligands that in the future may be used as anticancer drugs. The mechanistic target of rapamycin (mTOR) is a protein kinase connected to several processes governing immunity, metabolism, cell development, and survival. The proliferation and metastasis of tumors have both been linked to the activation of the mTOR pathway. Female breast cancer represents about 15.3% of all new cancer cases in the U.S. alone and is frequently diagnosed among women aged 55 to 69 years. Given that the P13K/AKT/mTOR pathway is one of the most often activated in cancer, much attention has been paid to its resistance as a novel oncological treatment approach. mTOR/FRB Domain’s recruitment cleft as, well as substrate recruitment mechanism, was targeted using a structural-based approach. A series of selective inhibitory small molecules have been designed and screened for the best inhibiting target binding triad of the FRB Domain with better ADME and no detectable toxic effects.

In-silico designing of an inhibitor against mTOR FRB domain Therapeutic impli...

Dr Varruchi Sharma

Coronavirus disease 2019 (COVID-19) is a pandemic which had a severe impact on all aspects of life all over the world. Vaccines are the most significant and effective interventions which are capable enough to reduce the high burden of diseases around the globe. An effective vaccine is the most anticipated resolution. The hesitancy in general public towards vaccination is a major problem for Government and health authorities as well. In this study, evaluation of health issues faced after vaccination, preferred vaccines, role of health authorities in preventing the COVID 19 disease spread, and kind of hesitancy for vaccination are discussed. Primary random data is collected from 370 individuals from north India about the COVID vaccine. The descriptive and infernal statistical tools are implemented to analyze the data using SPSS software.

Acceptance and Attitudes of North Indian Population Towards COVID-19. 4-10-20...

Dr Varruchi Sharma

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