Unlocking the potential of oncology biomarkers: advancements in clinical theranostics.

INTRODUCTION: Cancer biomarkers have revolutionized the field of oncology by providing valuable insights into tumor changes and aiding in screening, diagnosis, prognosis, treatment prediction, and risk assessment. The emergence of "omic" technologies has enabled biomarkers to become reliable and accurate predictors of outcomes during cancer treatment. CONTENT: In this review, we highlight the clinical utility of biomarkers in cancer identification and motivate researchers to establish a personalized/precision approach in oncology. By extending a multidisciplinary technology-based approach, biomarkers offer an alternative to traditional techniques, fulfilling the goal of cancer therapeutics to find a needle in a haystack. SUMMARY AND OUTLOOK: We target different forms of cancer to establish a dynamic role of biomarkers in understanding the spectrum of malignancies and their biochemical and molecular characterization, emphasizing their prospective contribution to cancer screening. Biomarkers offer a promising avenue for the early detection of human cancers and the exploration of novel technologies to predict disease severity, facilitating maximum survival and minimum mortality rates. This review provides a comprehensive overview of the potential of biomarkers in oncology and highlights their prospects in advancing cancer diagnosis and treatment.

Revitalizing allicin for cancer therapy: advances in formulation strategies to enhance bioavailability, stability, and clinical efficacy.

The main objective of this review is to highlight the therapeutic potential of allicin, a defense molecule in garlic known for its diverse health benefits, and address the key challenges of its bioavailability and stability. The research further aims to evaluate various formulation strategies and nanotechnology-based delivery systems that can resolve these issues and improve allicin's clinical efficacy, especially in cancer therapy. We conducted a comprehensive review of the available literature and previous studies, focusing on the therapeutic properties of allicin, its bioavailability, stability issues, and novel formulation strategies. We assessed the mechanism of action of allicin in cancer, including its effects on signaling pathways, cell cycle, apoptosis, autophagy, and tumor development. We also evaluated the outcomes of both in vitro and in vivo studies on different types of cancers, such as breast, cervical, colon, lung, and gastric cancer. Despite allicin's significant therapeutic benefits, including cardiovascular, antihypertensive, cholesterol-lowering, antimicrobial, antifungal, anticancer, and immune-modulatory activity, its clinical utility is limited due to poor stability and unpredictable bioavailability. Allicin's bioavailability in the gastrointestinal tract is dependent on the activity of the enzyme alliinase, and its stability can be affected by various conditions like gastric acid and intestinal enzyme proteases. Recent advances in formulation strategies and nanotechnology-based drug delivery systems show promise in addressing these challenges, potentially improving allicin's solubility, stability, and bioavailability. Allicin offers substantial potential for cancer therapy, yet its application is hindered by its instability and poor bioavailability. Novel formulation strategies and nanotechnology-based delivery systems can significantly overcome these limitations, enhancing the therapeutic efficacy of allicin. Future research should focus on refining these formulation strategies and delivery systems, ensuring the safety and efficacy of these new allicin formulations. Clinical trials and long-term studies should be carried out to determine the optimal dosage, assess potential side effects, and evaluate their real-world applicability. The comparative analysis of different drug delivery approaches and the development of targeted delivery systems can also provide further insight into enhancing the therapeutic potential of allicin.

PROTAC: A Novel Drug Delivery Technology for Targeting Proteins in Cancer Cells.

The treatment measures of malignant carcinomas are most important for human health. In recent years the use of targeted therapy based on small molecule compounds and identical immunoglobulin has been the most frequently used tool to combat cancerous cells. But there are still several limitations in their clinical development and applications, including their ability to bind multiple molecular target sites, both cell surface receptors and intracellular proteins, promoting a greater risk of toxicity. PROTAC is a novel technology that maintains a balance between protein synthesis and degradation and uses molecules instead of conventional enzyme inhibitors, containing two active domains and a linker to destroy unwanted selective protein (like kinase, skeleton protein and regulatory protein). PROTACs are heterobifunctional nano molecules with a size range of about 10 nanometres that eliminate the protein complexes formed by protein-protein interaction through large and flat surfaces generally defined as "undruggable" in conventional drug delivery systems, which include around 85% of proteins present in humans, suggesting their wide application in the field of drug development. Such peptide-based PROTACs have successfully shown targets' destruction in cultured cells (e.g., MetAP-2, and FKBP12F36V, receptors for estrogens and androgen). However, some obstacles prevent this technology from transferring from the laboratory to its actual clinical utility, such as delivery system and bioavailability. The scope of the presented review is to give an overview of novel PROTAC technology with its limitations, advantages, mechanism of action, and development of photocontrolled PROTACs and to summarize its futuristic approach to targeting proteins in cancer cells.

Emergence of nutrigenomics and dietary components as a complementary therapy in cancer prevention.

Cancer is an illness characterized by abnormal cell development and the capability to infiltrate or spread to rest of the body. A tumor is the term for this abnormal growth that develops in solid tissues like an organ, muscle, or bone and can spread to other parts of the body through the blood and lymphatic systems. Nutrition is a critical and immortal environmental component in the development of all living organisms encoding the relationship between a person's nutrition and their genes. Nutrients have the ability to modify gene expression and persuade alterations in DNA and protein molecules which is researched scientifically in nutrigenomics. These interactions have a significant impact on the pharmacokinetic properties of bioactive dietary components as well as their site of action/molecular targets. Nutrigenomics encompasses nutrigenetics, epigenetics, and transcriptomics as well as other "omic" disciplines like proteomics and metabolomics to explain the vast disparities in cancer risk among people with roughly similar life style. Clinical trials and researches have evidenced that alternation of dietary habits is potentially one of the key approaches for reducing cancer risk in an individual. In this article, we will target how nutrigenomics and functional food work as preventive therapy in reducing the risk of cancer.

Bergenin ameliorates cognitive deficits and neuropathological alterations in sodium azide-induced experimental dementia.

Background: Bergenin, 4-O-methyl gallic acid glucoside, is a bioactive compound found in the cortex of Mallotus japonicus (L.f.) Müll.Arg. along with many other natural resources including that from Bergenia species. The present study delineates the neuroprotective potential of bergenin through the modulation of PPAR-γ receptors. Method: Dementia was induced in the Wistar rats by intraperitoneal (i.p.) administration of sodium azide (12.5 mg/kg for the first 5 days followed by 10 mg/kg for the next 9 days). The rats were then exposed to the Morris water maze test to assess the effect on cognitive abilities followed by a series of biochemical and histopathological evaluations. Results: Sodium azide-treated rats exhibited a severe deterioration of memory as suggested by poor performance in the spatial learning task in addition to the enhancement of brain acetylcholinesterase potential, oxidative stress, inflammation, and amyloid-ß (Aß) accumulation. Administration of bergenin to sodium azide-treated rats significantly recovered cognition and related biochemical variations. Further, co-administration of Bisphenol A diglycidyl ether (BADGE), a PPAR-γ antagonist with bergenin challenged its neuroprotective effects. Conclusions: The findings of our study exhibit that the cognitive restoration potential of bergenin may be attributed to its modulatory effects against cholinesterase, oxidative stress, and inflammatory markers, as well as its neuroprotective actions, thus aligning it as a possible therapy for Alzheimer's disease-related dementia. The study also fortifies the significance of PPAR-γ receptors in dementia.

Bioactive Based Nanocarriers for the Treatment of Viral Infections and SARS-CoV-2.

Since ancient times, plants have been used for their medicinal properties. They provide us with many phytomolecules, which serve a synergistic function for human well-being. Along with anti-microbial, plants also possess anti-viral activities. In Western nations, about 50% of medicines were extracted from plants or their constituents. The spread and pandemic of viral diseases are becoming a major threat to public health and a burden on the financial prosperity of communities worldwide. In recent years, SARS-CoV-2 has made a dramatic lifestyle change. This has promoted scientists not to use synthetic anti-virals, such as protease inhibitors, nucleic acid analogs, and other anti-virals, but to study less toxic anti-viral phytomolecules. An emerging approach includes searching for eco-friendly therapeutic molecules to develop phytopharmaceuticals. This article briefly discusses numerous bioactive molecules that possess anti-viral properties, their mode of action, and possible applications in treating viral diseases, with a special focus on coronavirus and various nano-formulations used as a carrier for the delivery of phytoconstituents for improved bioavailability.

The Genus Alternanthera: Phytochemical and Ethnopharmacological Perspectives.

Ethnopharmacological relevance: The genus Alternanthera (Amaranthaceae) comprises 139 species including 14 species used traditionally for the treatment of various ailments such as hypertension, pain, inflammation, diabetes, cancer, microbial and mental disorders. Aim of the review: To search research gaps through critical assessment of pharmacological activities not performed to validate traditional claims of various species of Alternanthera. This review will aid natural product researchers in identifying Alternanthera species with therapeutic potential for future investigation. Materials and methods: Scattered raw data on ethnopharmacological, morphological, phytochemical, pharmacological, toxicological, and clinical studies of various species of the genus Alternanthera have been compiled utilizing search engines like SciFinder, Google Scholar, PubMed, Science Direct, and Open J-Gate for 100 years up to April 2021. Results: Few species of Alternanthera genus have been exhaustively investigated phytochemically, and about 129 chemical constituents related to different classes such as flavonoids, steroids, saponins, alkaloids, triterpenoids, glycosides, and phenolic compounds have been isolated from 9 species. Anticancer, antioxidant, antibacterial, CNS depressive, antidiabetic, analgesic, anti-inflammatory, and immunomodulator effects have been explored in the twelve species of the genus. A toxicity study has been conducted on 3 species and a clinical study on 2 species. Conclusions: The available literature on pharmacological studies of Alternanthera species reveals that few species have been selected based on ethnobotanical surveys for scientific validation of their traditional claims. But most of these studies have been conducted on uncharacterized and non-standardized crude extracts. A roadmap of research needs to be developed for the isolation of new bioactive compounds from Alternanthera species, which can emerge out as clinically potential medicines.

An Overview of Phytotherapy Used in the Management of Type II Diabetes.

Diabetes mellitus is related to unconstrained high blood sugar and linked with long-term impairment, dysfunction and failure of several organs. Since 1980, the global frequency of diabetes has almost doubled in the adult population. In very rare cases due to poor prevention and management programs, diabetes causes worsening of health and reduced lifespan of the world population, thus impacting on the world's economy. Supplements, however, help in the improvement of nutritional deficiencies. Phytotherapeutics has the advantage of being economical and easy to access with marginal side effects. So, it is a preferred candidate for the management of diabetes. Currently, a multitude of pharmaceuticals are used which are obtained from natural sources having medicinal properties. The mechanistic approaches are based on the regulation of insulin signaling pathways, translocation of GLUT-4 receptors and/or activation of PPAR γ. These natural compounds include numerous flavonoids which help in preventing glucose absorption by preventing the absorption of α-amylase and α-glucosidase. But to validate the efficacy and safety profile of these compounds, detailed validatory clinical studies are required. This review majorly focuses on the mechanistic approaches of various naturally derived compounds relevant for the condition of Diabetes Mellitus.

Isolation and estimation of flavonoid compound(s) of Baccharoides anthelmintica (L.) Moench.

Based on ethnobotanical surveys, an Indian traditional plant, i.e., Baccharoides anthelmintica (L.) Moench (Family - Asteraceae) was selected for detailed phytochemical investigations. B. anthelmintica seeds, purchased from local market, were extracted exhaustively in a Soxhlet apparatus using methanol as solvent. A well-established method was adopted to obtain phenolic compounds and flavonoids rich fraction of methanol extract. This fraction yielded two isolates (AK-1 and AK-2) upon purification by column chromatographic process. AK-1 was characterized as mixture of two isomeric compounds - 3',4',5,6,7- and 3',4',5,7,8-pentahydroxy flavanone, and AK-2 as butein (chalcone derivative) by UV, IR and NMR spectral analysis. A TLC densitometric method was developed and validated to estimate the content of butein in B. anthelmintica seeds, and was found to be 1.252 mg/g. Bioactive Marker (butein) based standardized B. anthelmintica seeds will ensure reproducibility in efficacy and safety of the plant or authenticity of its products.

Bergenin - A Biologically Active Scaffold: Nanotechnological Perspectives.

Bergenin, 4-O-methyl gallic acid glucoside, is a bioactive compound in various plants belonging to different families. The present work compiles scattered information on pharmacology, structure-activity relationship and nanotechnological aspects of bergenin, collected from various electronic databases such as Sci Finder, PubMed, Google Scholar, etc. Bergenin has been reported to exhibit hepatoprotective, anti-inflammatory, anticancer, neuroprotective, antiviral, and antimicrobial activities. Molecular docking studies have shown that isocoumarin pharmacophore of bergenin is essential for its bioactivities. Bergenin holds a great potential to be used as a lead molecule and also as a therapeutic agent for the development of more efficacious and safer semisynthetic derivatives. Nanotechnological concepts can be employed to overcome the poor bioavailability of bergenin. Finally, it is concluded that bergenin can emerge as clinically potential medicine in modern therapeutics.

Natural Product-Based Studies for the Management of Castration-Resistant Prostate Cancer: Computational to Clinical Studies.

Background: With prostate cancer being the fifth-greatest cause of cancer mortality in 2020, there is a dire need to expand the available treatment options. Castration-resistant prostate cancer (CRPC) progresses despite androgen depletion therapy. The mechanisms of resistance are yet to be fully discovered. However, it is hypothesized that androgens depletion enables androgen-independent cells to proliferate and recolonize the tumor. Objectives: Natural bioactive compounds from edible plants and herbal remedies might potentially address this need. This review compiles the available cheminformatics-based studies and the translational studies regarding the use of natural products to manage CRPC. Methods: PubMed and Google Scholar searches for preclinical studies were performed, while ClinicalTrials.gov and PubMed were searched for clinical updates. Studies that were not in English and not available as full text were excluded. The period of literature covered was from 1985 to the present. Results and Conclusion: Our analysis suggested that natural compounds exert beneficial effects due to their broad-spectrum molecular disease-associated targets. In vitro and in vivo studies revealed several bioactive compounds, including rutaecarpine, berberine, curcumin, other flavonoids, pentacyclic triterpenoids, and steroid-based phytochemicals. Molecular modeling tools, including machine and deep learning, have made the analysis more comprehensive. Preclinical and clinical studies on resveratrol, soy isoflavone, lycopene, quercetin, and gossypol have further validated the translational potential of the natural products in the management of prostate cancer.

Uncurtaining the effect of COVID-19 in diabetes mellitus: a complex clinical management approach.

The aim of the present review is to overview the common properties of corona virus and hence proofs well beginning of corona virus in persons with diabetes, and its treatment. Globally, it has been observed that according to the statistics, India has the second largest number of people with diabetes. Literature review has been implemented within the databases using suitable keywords. For persons suffering from diabetic disorder, the COVID-19 infection becomes a dual challenge. Diabetes is a severe metabolic situation which causes the sugar levels in the blood to increase than the normal level. Normally, communicable disease like COVID-19 is more prevailing in patients with diabetes. Diabetic patient has poor immune response to infections. The different bacterial, viral, parasitic, and mycotic infections showed increased probability in diabetic patients as compared to non-diabetic patient. All these conclusions clear out the intention that the diabetic patients are more susceptible to enhanced inflammatory response that may lead to rapid spreading of COVID-19 infection with high rate of mortality. In the present situation of pandemic, managing diabetes seems to be quite challenging and diabetic patient having COVID-19 infection should follow normal course of antihypertensive and antidiabetic drugs prescribed with the exception of sodium glucose co-transpoters-2 inhibitors which would increase the risk of dehydration and ketoacidosis. In view of above discussion, this article highlights the proposed mechanism of COVID-19 infection linking it with diabetes, antidiabetic drugs to be used in COVID-19 infection along with their advantages, and disadvantages and management of COVID-19 infection diabetic patient.

Role of Natural Products in the Treatment of Obesity: Nanotechnological Perspectives.

Obesity is a major disorder characterized by excessive fat in the body. Various factors responsible for obesity are dietary, lifestyle, genetic, and environmental factors. The last two decades witnessed an enormous increase in obesity and its comorbidities among people worldwide, thus making it the fifth major cause of human death. As per the recent report of WHO, a total of 38 million children (age < 5 years) were overweight or obese in 2019, and according to the Organization for Economic Cooperation and Development (OECD) report, almost 1 in 4 people are obese. For the treatment of obesity, various synthetic drugs are available but on the other side, these are associated with severe adverse effects. To overcome this problem and in the view of the current situation, researchers emphasize more on the development of natural products for the management of obesity. Primary and secondary metabolites like polyphenols, alkaloids, saponins, and flavonoids derived from various plants worldwide are used to develop a formulation for the management of obesity. The phytoconstituents exert their action by suppressing the proliferation of adipocytes, inducing apoptosis of adipocytes, inhibiting lipogenesis, activating lipases, stimulating fatty acid ß-oxidation, diminishing inflammatory responses, or conquering oxidative stress. This review also highlights the importance of the nanoencapsulation technique which enhances the efficacy of phytoconstituents by improving solubility, stability, and bioavailability to fight against obesity and comorbidity.

Screening of Alkaloidal Fraction of Conium maculatum L. Aerial Parts for Analgesic and Antiinflammatory Activity.

Conium maculatum Linn. (Umbelliferae) has been traditionally used in the treatment of spasmodic disorders, and to relieve nervous excitation, rheumatic pains in the old and feeble, pain in stomach, pain of gastric ulcer, nervousness and restlessness. Alkaloids have long been considered as bioactive group of constituents present in C. maculatum. Despite a long tradition of use, C. maculatum has not been evaluated pharmacologically to validate its traditional claims for analgesic and antiinflammatory activities. Thus, the present investigations were undertaken with an objective to evaluate alkaloidal fraction of C. maculatum aerial parts for analgesic and antiinflammatory activities. Test doses (100 or 200 mg/kg, p.o.) of alkaloidal fraction were evaluated for analgesic activity using tail flick test and antiinflammatory activity using carrageenan-induced paw oedema test in rats. Morphine (5 mg/kg, p.o.) and indomethacin (5 mg/kg, p.o.) were used as standard analgesic and antiinflammatory drugs, respectively. Alkaloidal fraction of the plant exhibited significant analgesic activity at a dose of 200 mg/kg as it showed significant increase in tail flicking reaction time with respect to the control during 2 h intervals of observation. It also exhibited significant antiinflammatory activity at a dose of 200 mg/kg as it inhibited paw oedema in rats to 71% and reduced the paw volume one-fourth to the control during 1(st) h of the study. The present investigations suggest that alkaloids are responsible for analgesic and antiinflammatory activities of C. maculatum.

Anticonvulsant potential of holy basil, Ocimum sanctum Linn., and its cultures.

Callus cultures from stem of O. sanctum were induced on slightly modified Murashige and Skoog's (MS) medium and supplemented with 2,4-dichlorophenoxyacetic acid (2,4-D, 1-2 ppm) and kinetin (kn, 1 ppm). Different extractives of stem, leaf and stem callus of O. sanctum were tested for anticonvulsant activity against standard drug phenytoin using maximal electroshock (MES) model. Ethanol and chloroform extractives of stem, leaf and stem calli were effective in preventing tonic convulsions induced by transcorneal electroshock.