Current Trends in the Biomarker'sDiscovery for the Treatment and Management of Colorectal Cancer: A ComprehensiveReview.

Colorectal cancer (CRC) is a significant health issue, with countless individuals suffering. With its bleak outlook, the number of deaths caused by CRC can only be reduced if new diagnostic and prognostic biomarkers are identified and developed quickly. Recent developments in screening programme development and patient management have been encouraging, but many unanswered questions still need to be addressed before a customized colorectal cancer approach can be implemented. Prevention of diseases, the detection of them in their early stages, the analysis of the severity, and the treatment of any metastasized diseases are all paramount. Despite the increased utilization of genetic profiles in decision-making processes, such as the selection of therapy and predicting drug response, there are only a limited number of validated biomarkers for colorectal cancer that are suitable for clinical practice. To further research into colorectal carcinogenesis, pinpoint prospective indicators, and validate these indicators, creating non-intrusive, sensitive, and exact biomarkers is an urgent requirement. This procedure is reliant on translational proteomics. This investigation serves as a comprehensive resource on the current state of genetic and epigenetic biomarkers in diagnosing, predicting, and evaluating colorectal cancer. It underscores the transformative potential of these biomarkers in advancing CRC patient care, from early detection to personalized treatment strategies. However, it also underscores the need for ongoing research and validation to realize their clinical utility fully.

Revolutionizing Cancer Treatment: Unleashing the Power of Viral Vaccines, Monoclonal Antibodies, and Proteolysis-Targeting Chimeras in the New Era of Immunotherapy.

In the realm of cancer immunotherapy, a profound evolution has ushered in sophisticated strategies that encompass both traditional cancer vaccines and emerging viral vaccines. This comprehensive Review offers an in-depth exploration of the methodologies, clinical applications, success stories, and future prospects of these approaches. Traditional cancer vaccines have undergone significant advancements utilizing diverse modalities such as proteins, peptides, and dendritic cells. More recent innovations have focused on the physiological mechanisms enabling the human body to recognize and combat precancerous and malignant cells, introducing specific markers like peptide-based anticancer vaccines targeting tumor-associated antigens. Moreover, cancer viral vaccines, leveraging engineered viruses to stimulate immune responses against specific antigens, exhibit substantial promise in inducing robust and enduring immunity. Integration with complementary therapeutic methods, including monoclonal antibodies, adjuvants, and radiation therapy, has not only improved survival rates but also deepened our understanding of viral virulence. Recent strides in vaccine design, encompassing oncolytic viruses, virus-like particles, and viral vectors, mark the frontier of innovation. While these advances hold immense potential, critical challenges must be addressed, such as strategies for immune evasion, potential off-target effects, and the optimization of viral genomes. In the landscape of immunotherapy, noteworthy innovations take the spotlight from the use of immunomodulatory agents for the enhancement of innate and adaptive immune collaboration. The emergence of proteolysis-targeting chimeras (PROTACs) as precision tools for cancer therapy is particularly exciting. With a focus on various cancers, from melanoma to formidable solid tumors, this Review critically assesses types of cancer vaccines, mechanisms, barriers in vaccine therapy, vaccine efficacy, safety profiles, and immune-related adverse events, providing a nuanced perspective on the underlying mechanisms involving cytotoxic T cells, natural killer cells, and dendritic cells. The Review also underscores the transformative potential of cutting-edge technologies such as clinical studies, molecular sequencing, and artificial intelligence in advancing the field of cancer vaccines. These tools not only expedite progress but also emphasize the multidimensional and rapidly evolving nature of this research, affirming its profound significance in the broader context of cancer therapy.

Antidiarrheal activity of Clitorea ternatea Linn. (Fabaceae) ethanol leaf extract in rats.

BACKGROUND: Clitorea ternatea Linn. (Fabaceae) is a plant which is traditionally used for the treatment of wide range of pharmacological activities including antimicrobial, antipyretic, anti-inflammatory, analgesic, diuretic, local anesthetic, antidiabetic, insecticidal, blood platelet aggregation-inhibiting and diarrhea in India. However, scientific evidence does not exist in any literature to corroborate the claim of therapeutic success of the plant species in diarrhea. AIM OF THE STUDY: The core aim of the present study is to evaluate the antidiarrheal activity of C. ternatea ethanol extract (CTE). MATERIALS AND METHODS: The antidiarrheal activity was evaluated using castor oil and magnesium sulfate (MgSO4)-induced diarrhea method. The effects of CTE on gastrointestinal motility, intestinal transit and enteropooling were also examined in rats. RESULTS: CTE (100-400 mg/kg, p.o.) produced dose-dependent and significant (P < 0.05-0.01) protection of rats against castor oil and MgSO4-induced diarrhea, inhibited intestinal transit and delayed gastric emptying. CTE dose dependently and significantly delayed the onset of castor oil and MgSO4-induced diarrhea, decreased the frequency of defecation and reduced the severity of diarrhea in the rats compared with loperamide (10 mg/kg, p.o.). CONCLUSION: These findings confirm the ethno medicinal use of C. ternatea as a valuable natural remedy for the treatment, management and/or control of diarrhea.

Microwave Assisted Synthesis of 1-[5-(Substituted Aryl)-1H-Pyrazol-3-yl]-3,5-Diphenyl-1H-1,2,4-Triazole as Antinociceptive and Antimicrobial Agents.

PURPOSE: An efficient technique has been developed for microwave assisted synthesis of 1-[5-(substituted aryl)-1H-pyrazol-3-yl]-3,5-diphenyl-1H-1,2,4-triazole as antinociceptive and antimicrobial agents. METHODS: The desired compounds (S1-S10) were synthesized by the microwave irradiation via cyclization of formerly synthesized chalcones of 3,5-diphenyl-1H-1,2,4-triazole and hydrazine hydrate in mild acidic condition. All newly synthesized compounds were subjected to study their antinociceptive and antimicrobial activity. The analgesic potential of compounds was tested by acetic acid induced writhing response and hot plate method. The MIC values for antimicrobial activity were premeditated by liquid broth method. RESULTS: The compounds S1, S2, S4, S6 and S10 were found to be excellent peripherally acting analgesic agents when tested on mice by acetic acid induced writhing method and compounds S3, S6 and S1 at dose level of 100 mg/kg were exhibited superior centrally acting antinociceptive activity when tested by Eddy's hot plate method. In antimicrobial activity compound S10 found to be broad spectrum antibacterial agent at MIC value of 15.62 µg/ml and compound S6 was exhibited antifungal potential at 15.62 µg/mL on both fungal strains. CONCLUSION: Some novel pyrazoles clubbed with 1,2,4-triazole derivatives were synthesized and evaluated as possible antimicrobial, centrally and peripherally acting analgesics.

Analgesic activity of some 1,2,4-triazole heterocycles clubbed with pyrazole, tetrazole, isoxazole and pyrimidine.

PURPOSE: In the present study in vivo analgesic activity of some previously synthesized 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine ring have been evaluated. METHODS: Acetic acid induced writhing method and Hot plate method has been described to study analgesic activity of some 1,2,4-triazole derivatives containing pyrazole, tetrazole, isoxazole and pyrimidine as a pharmacological active lead. RESULTS: Thirty six different derivatives containing 1,2,4-triazole ring were subjected to study their in vivo analgesic activity. Chloro, nitro and methoxy, hydroxy and bromo substituted derivatives showed excellent analgesic activity and dimethylamino, furan and phenyl substituted derivatives showed moderate analgesic activity in both of the methods. Compounds IIIa, IIId, IIIf, IIIi, IIIj, IVa, IVb, IVd, IVf, IVh, IVj IV3a and IIj were found to be superior analgesic agents after screening by Acetic acid induced writhing method. Compounds IIIb, IIId, IIIf, IIIh, IIIj, IVa, IVb, IVd, IVf, IVh, IVi, IV3c, IV3e and IIj were showed analgesic potential after screening of Hot plate method. CONCLUSION: All tested compounds containing 1,2,4-triazole were found to be promising analgesic agents, for this activity pyrazole, tetrazole, isoxazole and pyrimidine leads might be supported.

Anti-hyperglycaemic and lipid lowering potential of Adenanthera pavonina Linn. in streptozotocin induced diabetic rats.

In India, Adenanthera pavonina is traditionally used in the treatment of diabetes mellitus and lipid disorders. In the present study, the antihyperglycaemic and lipid lowering effect of Adenanthera pavonina seed aqueous extract (APSAE) was evaluated using streptozotocin induced diabetes in rats. Streptozotocin was given at the dose of 55 mg/kg, i.p. After induction of diabetes, APSAE was administered for 30 days p. o. and simultaneously different biochemical parameters like plasma glucose, HbA1c, serum triglyceride, cholesterol, LDL-cholesterol and HDL-cholesterol were estimated. Diabetic control showed significant increase (P < 0.01) in plasma glucose, serum triglyceride, cholesterol, LDL-cholesterol and significant decrease (P < 0.01) in serum HDL-cholesterol and HbA1c. Treatment with APSAE showed significant reduction (P < 0.01) in plasma glucose when compared with diabetic control. The elevated levels of serum triglyceride and cholesterol levels were significantly reduced (P < 0.01) by APSAE. APSAE treatment for 30 days showed significant decrease in serum LDL-cholesterol (P < 0.01) and significant increase in serum HDL cholesterol level (P < 0.01). Moreover, diabetic control there was significant decrease in HbA1c which was significantly increased (P < 0.05) by treatment with APSAE. Hence, from the result obtained in the present study it can be confirmed that Adenanthera pavonina has the potential to treat diabetes condition and associated lipid disorders.

Attenuating effect of seeds of Adenanthera pavonina aqueous extract in neuropathic pain in streptozotocin-induced diabetic rats: an evidence of neuroprotective effects

The aim of present study was to investigate the attenuating effects of Adenanthera pavonina L., Leguminosae-Mimosaceae seeds aqueous extract (APSAE), in streptozotocin (STZ)-induced diabetic neuropathy in rats. APSAE (50, 100 and 200 mg/kg per day) was given to diabetic rats for twelve weeks. Cold and hot water tail immersion tests, photoactometer and Rota-rod tests were performed to assess degree of colder, thermal, spontaneous motor activity and motor co-ordination changes respectively at different time intervals i.e., week 0, 4, 8 and 12. Tissue superoxide anion and total calcium levels were determined after twelve weeks to assess biochemical alterations. Histopathological evaluations of sciatic nerve were also performed to assess nerve damage. APSAE treatment increased tail flick latency significantly in diabetic rats. APSAE also reduced superoxide anion and total calcium levels. These results suggested that APSAE has attenuated development of diabetic neuropathy in streptozotocin-induced diabetic rats when compared with pregabalin (10 mg/kg, p.o.) and could be beneficial in preventing the progression of diabetic nephropathy.

Extract of Adenanthera pavonina L. seed reduces development of diabetic nephropathy in streptozotocin-induced diabetic rats.

OBJECTIVE: The aim of the present study was to investigate the renal protective effect of Adenanthera pavonina (A. pavonina) seed aqueous extract (APSAE), in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: The renal protective effect of A. pavonina seed aqueous extract (APSAE) was studied in STZ-induced diabetic rats. APSAE (50, 100 and 200 mg/kg per day) was given daily to diabetic rats for 13 weeks. Blood glucose, serum parameters such as albumin, creatinine, total protein, urea, lipid profile, glycated haemoglobin (HbA1c), and urine parameters such as urine protein and albumin were examined. Kidney histopathology was also done. RESULTS: After 13 weeks of treatment, in STZ-induced diabetic rats, severe hyperglycemia was developed, with marked increase in proteinuria and albuminuria. However, APSAE treatment significantly reduced proteinuria, albuminuria, lipid levels, and HbA1c deposition in diabetic rats. CONCLUSION: These results suggested that APSAE has reduced development of diabetic nephropathy in streptozotocin-induced diabetic rats and could have beneficial effect in reducing the progression of diabetic nephropathy.

Synthesis and pharmacological evaluation of some new pyrimidine derivatives containing 1,2,4-triazole.

PURPOSE: An efficient method has been described for synthesis of 6-(substituted aryl)-4-(3,5-diphenyl-1H-1,2,4-triazol-1-yl)-1, 6-dihydropyrimidine-2-thiol, as a beneficial antimicrobial, anticonvulsant and anticancer agents. METHODS: The clalcones of title compounds were synthesized in three steps and subsequently these chalcones were further reacted with thiourea in the presence of KOH in ethanol, which led to the formation of dihydropyrimidine derivatives (4a-j). Compounds 4a-j were screened for their in vitro antimicrobial activity by agar well method and their anticonvulsant activity by the MES model. Anticancer activity of two newly synthesized heterocycles were evaluated at National Cancer Institute (NCI) Maryland, USA against 60 cell lines of different human tumor at a single dose of 10(-5) M. RESULTS: Compound 4b, 4c, 4d, 4i and 4j were exhibited significant antimicrobial potential against tested strains at 50µg/ml and 100µg/ml concentrations. Out of the ten compounds studied 4a, 4b, 4c, 4h and 4j showed comparable MES activity to Phenytoin and Carbamazepine after 0.5h. Tested compounds did not showed to be more potent than standard drugs after 4h. Compound 4a and 4d were found active on Non-Small Cell Lung Cancer (HOP-92). CONCLUSION: Ten noveldihydropyrimidine analogues has been synthesized, characterized and found to bepromising antibacterial, anticonvulsant and antitumor agents.

Antidiabetic Activity of Aqueous Leaves Extract of Sesbania sesban (L) Merr. in Streptozotocin Induced Diabetic Rats.

The aqueous leaves extract of Sesbania sesban (L) Merr. (Family: Fabaceae) was evaluated for its antidiabetic potential on normal and streptozotocin (STZ)-induced diabetic rats. In the chronic model, the aqueous extract was administered to normal and STZ- induced diabetic rats at the doses of 250 and 500 mg/kg body weight (b.w.) p.o. per day for 30 days. The fasting Blood Glucose Levels (BGL), serum insulin level and biochemical data such as glycosylated hemoglobin, Total Cholesterol (TC), Triglycerides (TG), High Density Lipoproteins (HDL) and Low Density Lipoproteins (LDL) were evaluated and all were compared to that of the known anti-diabetic drug glibenclamide (0.25 mg/kg b.w.). The statistical data indicated significant increase in the body weight, liver glycogen, serum insulin and HDL levels and decrease in blood glucose, glycosylated hemoglobin, total cholesterol and serum triglycerides when compared with glibenclamide. Thus the aqueous leaves extract of Sesbania sesban had beneficial effects in reducing the elevated blood glucose level and lipid profile of STZ-induced diabetic rats.