New insights into molecular signaling pathways and current advancements in prostate cancer diagnostics & therapeutics.

Prostate adenocarcinoma accounts for more than 20% of deaths among males due to cancer. It is the fifth-leading cancer diagnosed in males across the globe. The mortality rate is quite high due to prostate cancer. Despite the fact that advancements in diagnostics and therapeutics have been made, there is a lack of effective drugs. Metabolic pathways are altered due to the triggering of androgen receptor (AR) signaling pathways, and elevated levels of dihydrotestosterone are produced due to defects in AR signaling that accelerate the growth of prostate cancer cells. Further, PI3K/AKT/mTOR pathways interact with AR signaling pathway and act as precursors to promote prostate cancer. Prostate cancer therapy has been classified into luminal A, luminal B, and basal subtypes. Therapeutic drugs inhibiting dihydrotestosterone and PI3K have shown to give promising results to combat prostate cancer. Many second-generation Androgen receptor signaling antagonists are given either as single agent or with the combination of other drugs. In order to develop a cure for metastasized prostate cancer cells, Androgen deprivation therapy (ADT) is applied by using surgical or chemical methods. In many cases, Prostatectomy or local radiotherapy are used to control metastasized prostate cancer. However, it has been observed that after 1.5 years to 2 years of Prostatectomy or castration, there is reoccurrence of prostate cancer and high incidence of castration resistant prostate cancer is seen in population undergone ADT. It has been observed that Androgen derivation therapy combined with drugs like abiraterone acetate or docetaxel improve overall survival rate in metastatic hormone sensitive prostate cancer (mHSPC) patients. Scientific investigations have revealed that drugs inhibiting poly ADP Ribose polymerase (PARP) are showing promising results in clinical trials in the prostate cancer population with mCRPC and DNA repair abnormalities. Recently, RISUG adv (reversible inhibition of sperm under guidance) has shown significant results against prostate cancer cell lines and MTT assay has validated substantial effects of this drug against PC3 cell lines. Current review paper highlights the advancements in prostate cancer therapeutics and new drug molecules against prostate cancer. It will provide detailed insights on the signaling pathways which need to be targeted to combat metastasized prostate cancer and castration resistant prostate cancer.

Application of biosensors in cancers, an overview.

The deadliest disease in the world, cancer, kills many people every year. The early detection is the only hope for the survival of malignant cancer patients. As a result, in the preliminary stages of, the diagnosis of cancer biomarkers at the cellular level is critical for improving cancer patient survival rates. For decades, scientists have focused their efforts on the invention of biosensors. Biosensors, in addition to being employed in other practical scenarios, can essentially function as cost effective and highly efficient devices for this purpose. Traditional cancer screening procedures are expensive, time-consuming, and inconvenient for repeat screenings. Biomarker-based cancer diagnosis, on the other hand, is rising as one of the most potential tools for early detection, disease progression monitoring, and eventual cancer treatment. As Biosensor is an analytical device, it allows the selected analyte to bind to the biomolecules being studied (for example RNA, DNA, tissue, proteins, and cells). They can be divided based on the kind of biorecognition or transducer elements on the sensor. Most biosensor analyses necessitate the analyte being labeled with a specific marker. In this review article, the application of distinct variants of biosensors against cancer has been described.

The Discovery of Novel Antimicrobial Agents through the Application of Isocyanide-Based Multicomponent Reactions.

Multicomponent reactions (MCR) have been used to synthesize a wide range of analogs from several classes of heterocyclic compounds, with multifaceted medicinal uses. The synthesis of highly functionalized molecules in a single pot is a unique property of MCR, allowing researchers to quickly assemble libraries of compounds of biological interest and uncover novel leads as possible therapeutic agents. Isocyanide-based multicomponent reactions have proven to be extremely effective at swiftly specifying members of compound libraries, particularly in the discovery of drugs. The understanding of structure-activity correlations that drive the development of new goods and technology requires structural variety in these libraries. In today's world, antibiotic resistance is a major ongoing problem that poses risks to public health. The implementation of isocyanide-based multicomponent reactions upholds a significant potential in this regard. By utilizing such reactions, new antimicrobial compounds can be discovered and subsequently used to fight against such concerns. This study discusses the recent developments in antimicrobial medication discovery using isocyanide-based multicomponent reactions (IMCRs). Furthermore, the article emphasizes the potential of IMCRs (Isocyanide-based multicomponent based reactions) in the near future.

The Emerging Role of Epigenetics in Metabolism and Endocrinology.

Each cell in a multicellular organism has its own phenotype despite sharing the same genome. Epigenetics is a somatic, heritable pattern of gene expression or cellular phenotype mediated by structural changes in chromatin that occur without altering the DNA sequence. Epigenetic modification is an important factor in determining the level and timing of gene expression in response to endogenous and exogenous stimuli. There is also growing evidence concerning the interaction between epigenetics and metabolism. Accordingly, several enzymes that consume vital metabolites as substrates or cofactors are used during the catalysis of epigenetic modification. Therefore, altered metabolism might lead to diseases and pathogenesis, including endocrine disorders and cancer. In addition, it has been demonstrated that epigenetic modification influences the endocrine system and immune response-related pathways. In this regard, epigenetic modification may impact the levels of hormones that are important in regulating growth, development, reproduction, energy balance, and metabolism. Altering the function of the endocrine system has negative health consequences. Furthermore, endocrine disruptors (EDC) have a significant impact on the endocrine system, causing the abnormal functioning of hormones and their receptors, resulting in various diseases and disorders. Overall, this review focuses on the impact of epigenetics on the endocrine system and its interaction with metabolism.

Molecular and therapeutic effect of CRISPR in treating cancer.

Cancer has become one of the common causes of mortality around the globe due to mutations in the genome which allows rapid growth of cells uncontrollably without repairing DNA errors. Cancers could arise due alterations in DNA repair mechanisms (errors in mismatch repair genes), activation of oncogenes and inactivation of tumor suppressor genes. Each cancer type is different and each individual has a unique genetic change which leads them to cancer. Studying genetic and epigenetic alterations in the genome leads to understanding the underlying features. CAR T therapy over other immunotherapies such as monoclonal antibodies, immune checkpoint inhibitors, cancer vaccines and adoptive cell therapies has been widely used to treat cancer in recent days and gene editing has now become one of the promising treatments for many genetic diseases. This tool allows scientists to change the genome by adding, removing or altering genetic material of an organism. Due to advance in genetics and novel molecular techniques such as CRISPR, TALEN these genes can be edited in such a way that their original function could be replaced which in turn improved the treatment possibilities and can be used against malignancies and even cure cancer in future along with CAR T cell therapy due to the specific recognition and attacking of tumor.

Chickpea Peptide: A Nutraceutical Molecule Corroborating Neurodegenerative and ACE-I Inhibition.

Chickpea seeds are the source of proteins in human nutrition and attribute some nutraceutical properties. Herein, we report the effects of chickpea seed bioactive peptide on albumin, insulin, lactoglobulin and lysozyme amyloid fibril formation. Employing thioflavin T (ThT) assays and circular dichroism (CD), amyloid structural binding transition was experimented to analyze the inhibition of amyloid fibril formation. The purified active peptide with a molecular mass of 934.53 Da was evaluated in vitro for its ACE-I inhibitory, antibacterial, antifungal and antidiabetic activities. Further, in vivo animal studies were carried out in wistar rats for blood pressure lowering action. In hypertensive rats, chickpea peptide decreased 131 ± 3.57 mm of Hg for systolic blood pressure and 86 ± 1.5 mm of Hg for diastolic blood pressure after 8 h intraperitoneal administration. Additionally, the peptide suppressed the fibrillation of amyloid and destabilized the preformed mature fibrils. Data emphasize efficacy of chickpea peptide vis-a-vis ACE-Inhibitory, antibacterial, antifungal, antidiabetic and anti-amyloidogenic activities, allowing us to propose this novel peptide as a suitable candidate for nutraceutical-based drugs and seems the first kind of its nature.

In vitro cytotoxicity and anti-cancer drug release behavior of methionine-coated magnetite nanoparticles as carriers.

A novel and specific drug delivery for in vitro cancer targeted are developed successfully by a simple one-step method. A CoFe2O4@Methionine core-shell nanoparticle was prepared by the reflux assay which amino acid in the surface makes ferrite biocompatible, enhances its chemical stability, and improves the drug-loading capacity. The synthesized nanoparticles were characterized using FTIR, TGA, XRD, SEM, TEM, and VSM which coating amino acid on the surface of CoFe2O4 was confirmed by XRD and TGA. The appearance of a new peak for C≡N confirms the formation of Letrozole-loaded carrier in the FTIR. The vibrating sample magnetometer of both bare CoFe2O4 and Methionine-coated CoFe2O4 nanoparticles exhibited room-temperature superparamagnetic behavior with a saturation value of 46 emu/g and 16.8 emu/g, respectively. The morphology and size of samples were characterized by SEM and TEM that the average size of the particle was around 28-29 nm. The loading of Letrozole and the effect of pH (5, 7.4) on the release behavior of the carrier was studied. The result of the drug release in pH is equal to 5 was about 88% which higher than pH is equal to 7.4. Also, the preparation had been evaluated for determining its cytotoxicity using MCF-7, MDA-MB-231, and MCF10A cells as an in vitro model, and the result vitro experiments showed that CoFe2O4@Methionine could significantly reduce cancer in cells model. These results demonstrate that core-shell nanoparticle was prepared is biocompatible and have potential use as drug delivery.

Anti-cancer activity of human gastrointestinal bacteria.

Malignant neoplasm is one of the most incurable diseases among inflammatory diseases. Researchers have been studying for decades to win over this lethal disease and provide the light of hope to humankind. The gastrointestinal bacteria of human hold a complex ecosystem and maintain homeostasis. One hundred trillion microbes are residing in the gastrointestinal tract of human. Disturbances in the microbiota of human's gastrointestinal tract can create immune response against inflammation and also can develop diseases, including cancer. The bacteria of the gastrointestinal tract of human can secrete a variety of metabolites and bioproducts which aid in the preservation of homeostasis in the host and gut. During pathogenic dysbiosis, on the other hand, numerous microbiota subpopulations may increase and create excessive levels of toxins, which can cause inflammation and cancer. Furthermore, the immune system of host and the epithelium cell can be influenced by gut microbiota. Probiotics, which are bacteria that live in the gut, have been protected against tumor formation. Probiotics are now studied to see if they can help fight dysbiosis in cancer patients undergoing chemotherapy or radiotherapy because of their capacity to maintain gut homeostasis. Countless numbers of gut bacteria have demonstrated anti-cancer efficiency in cancer treatment, prevention, and boosting the efficiency of immunotherapy. The review article has briefly explained the anti-cancer immunity of gut microbes and their application in treating a variety of cancer. This review paper also highlights the pre-clinical studies of probiotics against cancer and the completed and ongoing clinical trials on cancers with the two most common and highly effective probiotics Lactobacillus and Bacillus spp.

TNFR2 antagonist and agonist: a potential therapeutics in cancer immunotherapy.

Tumour necrosis factor receptor 2 or TNFR2 is considered an appealing target protein due to its limited frequency to TREGs, which are highly immunosuppressive and present on human malignancies. Numerous studies have revealed that TNFR2 is primarily found on MDSCs (myeloid-derived suppressor cells) and CD + Foxp3 + regulatory T cells (TREGs). Therefore, it has great importance in the proliferation and functional activity of TREGs and MDSCs. TNFR2 suppression must be downregulated or upregulated as required to treat malignancies and diseases like autoimmune disorders. Therefore, at the molecular level, advances in the comprehension of TNFR2's complex structure and its binding to TNF have opened the door to structure-guided drug development. Two critical obstacles to cancer treatment are the dearth of TREG-specific inhibitors and the lack of widely applicable ways to target tumours via frequently expressed surface oncogenes directly. Many researchers have discovered potential antagonists and agonists of TNFR2, which were successful in inhibiting TREGs proliferation, reducing soluble TNFR2 secretion from normal cells, and expanding T effector cells. The data represented in the following review article elucidates the clinically administrated TNFR2 antagonist and agonist in treating cancers.

Niosomes: a novel targeted drug delivery system for cancer.

Recently, nanotechnology is involved in various fields of science, of which medicine is one of the most obvious. The use of nanoparticles in the process of treating and diagnosing diseases has created a novel way of therapeutic strategies with effective mechanisms of action. Also, due to the remarkable progress of personalized medicine, the effort is to reduce the side effects of treatment paths as much as possible and to provide targeted treatments. Therefore, the targeted delivery of drugs is important in different diseases, especially in patients who receive combined drugs, because the delivery of different drug structures requires different systems so that there is no change in the drug and its effectiveness. Niosomes are polymeric nanoparticles that show favorable characteristics in drug delivery. In addition to biocompatibility and high absorption, these nanoparticles also provide the possibility of reducing the drug dosage and targeting the release of drugs, as well as the delivery of both hydrophilic and lipophilic drugs by Niosome vesicles. Since various factors such as components, preparation, and optimization methods are effective in the size and formation of niosomal structures, in this review, the characteristics related to niosome vesicles were first examined and then the in silico tools for designing, prediction, and optimization were explained. Finally, anticancer drugs delivered by niosomes were compared and discussed to be a suitable model for designing therapeutic strategies. In this research, it has been tried to examine all the aspects required for drug delivery engineering using niosomes and finally, by presenting clinical examples of the use of these nanocarriers in cancer, its clinical characteristics were also expressed.

A Systematic Review of Personalized Health Applications through Human-Computer Interactions (HCI) on Cardiovascular Health Optimization.

Introduction: Currently, the deployment of human-computer interactive technologies to provide personalized care has grown and immensely taken shape in most healthcare settings. With the increasing growth of the internet and technology, personalized health interventions including smartphones, associated apps, and other interventions demonstrate prowess in various health fields, including cardiovascular management. This systematic review thus examines the effectiveness of various human-computer interactions technologies through telehealth (mainly eHealth) towards optimizing the outcomes in cardiovascular treatment. Methods: A comprehensive search of MEDLINE, EMBASE, and CINAHL databases using key terms was conducted from 2000 to November 2021 to identify suitable studies that explored the use of human-computer interaction technologies to provide a personalized care approach to facilitate bolstered outcomes for cardiovascular patients, including the elderly. The included studies were assessed for quality and risk of bias, and the authors undertook a data extraction task. Results: Ten studies describing the use of a mix of personalized health app (mHealth) interventions were identified and included in the study. Among the included studies, nine of them were randomized trials. All of the studies demonstrated the effectiveness of various personalized health interventions in maximizing the benefits of cardiovascular disease treatment. Conclusions: Personalized health application interventions through precision medicine has great potential to boost cardiovascular disease management outcomes, including rehabilitation. Fundamentally, since each intervention's focus might differ based on the disease and outcome preference, it is recommended that more research be done to tailor the interventions to specific disease and patient outcome expectations.

Artificial intelligence and machine learning in precision and genomic medicine.

The advancement of precision medicine in medical care has led behind the conventional symptom-driven treatment process by allowing early risk prediction of disease through improved diagnostics and customization of more effective treatments. It is necessary to scrutinize overall patient data alongside broad factors to observe and differentiate between ill and relatively healthy people to take the most appropriate path toward precision medicine, resulting in an improved vision of biological indicators that can signal health changes. Precision and genomic medicine combined with artificial intelligence have the potential to improve patient healthcare. Patients with less common therapeutic responses or unique healthcare demands are using genomic medicine technologies. AI provides insights through advanced computation and inference, enabling the system to reason and learn while enhancing physician decision making. Many cell characteristics, including gene up-regulation, proteins binding to nucleic acids, and splicing, can be measured at high throughput and used as training objectives for predictive models. Researchers can create a new era of effective genomic medicine with the improved availability of a broad range of datasets and modern computer techniques such as machine learning. This review article has elucidated the contributions of ML algorithms in precision and genome medicine.

Telomerase gene therapy: a remission toward cancer.

Telomerase is an enzyme which is culpable for the aliment and stability of telomeres. It also maintains the genomic integrity and chromosomal stability. The progressive shortening of telomeres may cause chromosomal instability and alternation in the telomerase. It may cause telomere attrition which can lead to oncogenic incidence in human. Cancer is a disease which is induced by genetic alternations in genes. The genetic mutation within the hTERT is a common type of scenario which is generally found above 90% of cancer. In cancer, the length of telomere and the activity of telomerase are very important for cancer cells to proliferate and also for the survival of tumors. Cancer cells regulate through several pathways to increase telomerase activity. There have been several advancements developed to inhibit the telomerase activity in cancer cell but the repercussion of those have demonstrated many adverse effects. Research on AAVs-mediated telomerase gene therapy has demonstrated prominent outcomes in animal trials. Thus, it has the potential to bring significant shine in the telomerase cancer therapeutics. Here, in this review article, we have analyzed studies related to telomerase gene therapeutics to cure cancer. We also have summarized the telomerase function and mechanism of action to cause cancer. Moreover, other current development in the clinical advances of telomerase inhibition in cancer is described.

Elucidation of CRISPR-Cas9 application in novel cellular immunotherapy.

Novel cellular immunotherapy with engineered T cells has improved cancer treatment and established therapeutic promises to prevent tumor formation in clinical studies. Due to certain restrictions and difficulties, CAR and TCR T-cells therapies were inadequate at points. CRISPR Cas9 genome-editing tool has significant potential for these two cell-based therapies. As a specialized gene-editing technique, CRISPR Cas9 is used to repair genetic alternations with minimal damage. It is used as an adjunct to immunotherapy to stimulate a more robust immune response. CRISPR has long outpaced other target-specific genome editing methods such as ZFNs and TALEN because of its high efficiency, competence in targeting, and stable operating conditions. CRISPR can overcome the two major drawbacks of universal CAR T cells: allorejection and graft-vs-host disease. TCR-based T cell treatment can reduce inappropriate binding between endogenous and transgenic TCR, resulting in a reduction of severe toxicity. The CAR and TCR T based cell therapies uphold an excellent future for tumor malignancies. This article has elucidated the administration of CRISPR Cas9 in novel cellular immunotherapy, CAR, and TCR T cell therapy. However, this article did not fail to observe this technology's ethical concerns, limitations, and challenges. Furthermore, the article compares CRISPR-mediated allogeneic CAR T cell to TCR-T cell therapy.

An Overview of CAR T Cell Mediated B Cell Maturation Antigen Therapy.

Multiple Myeloma (MM) is one of the incurable types of cancer in plasma cells. While immense progress has been made in the treatment of this malignancy, a large percentage of patients were unable to adapt to such therapy. Additionally, these therapies might be associated with significant diseases and are not always tolerated well in all patients. Since cancer in plasma cells has no cure, patients develop resistance to treatments, resulting in R/R MM (Refractory/Relapsed Multiple Myeloma). BCMA (B cell maturation antigen) is primarily produced on mature B cells. It's up-regulation and activation are associated with multiple myeloma in both murine and human models, indicating that this might be an effective therapeutic target for this type of malignancy. Additionally, BCMA's predictive value, association with effective clinical trials, and capacity to be utilized in previously difficult to observe patient populations, imply that it might be used as a biomarker for multiple myeloma. Numerous kinds of BCMA-targeting medicines have demonstrated antimyeloma efficacy in individuals with refractory/relapsed MM, including CAR T-cell (Chimeric antigen receptor T cell) treatments, ADCs (Antibody-drug conjugate s), bispecific antibody constructs. Among these medications, CART cell-mediated BCMA therapy has shown significant outcomes in multiple myeloma clinical trials. This review article outlines CAR T cell mediated BCMA medicines have the efficiency to change the therapeutic pattern for multiple myeloma significantly.

Nanoparticles for Cancer Therapy: Current Progress and Challenges.

Cancer is one of the leading causes of death and morbidity with a complex pathophysiology. Traditional cancer therapies include chemotherapy, radiation therapy, targeted therapy, and immunotherapy. However, limitations such as lack of specificity, cytotoxicity, and multi-drug resistance pose a substantial challenge for favorable cancer treatment. The advent of nanotechnology has revolutionized the arena of cancer diagnosis and treatment. Nanoparticles (1-100 nm) can be used to treat cancer due to their specific advantages such as biocompatibility, reduced toxicity, more excellent stability, enhanced permeability and retention effect, and precise targeting. Nanoparticles are classified into several main categories. The nanoparticle drug delivery system is particular and utilizes tumor and tumor environment characteristics. Nanoparticles not only solve the limitations of conventional cancer treatment but also overcome multidrug resistance. Additionally, as new multidrug resistance mechanisms are unraveled and studied, nanoparticles are being investigated more vigorously. Various therapeutic implications of nanoformulations have created brand new perspectives for cancer treatment. However, most of the research is limited to in vivo and in vitro studies, and the number of approved nanodrugs has not much amplified over the years. This review discusses numerous types of nanoparticles, targeting mechanisms, and approved nanotherapeutics for oncological implications in cancer treatment. Further, we also summarize the current perspective, advantages, and challenges in clinical translation.