Murine Double Minute 2 (MDM2) inhibition is recognized as a potential preventive and therapeutic approach for several malignant neoplasms in humans. Targeting MDM2 is a viable strategy for cancer treatment, as it can be regulated by both p53-mediated and p53-independent pathways. Despite MDM2’s crucial role in carcinogenesis, research into pharmacological MDM2 inhibitors has been challenging. Since there are currently no FDA-approved MDM2 inhibitors available on the market, more research in this field is necessary. In several human cancer models, various natural substances have demonstrated the ability to inhibit MDM2. They include Glycyrrhizic Acid (GA), Parthenolide (PTL), chalcones, hoiamides, Isokotomolide A (IKA), Genistein (GT), Flavopiridol, Theaflavin (TF), Curcumin, Camellia sinensis (C.sinensis), and Sesquiterpene Lactones (STLs). Natural extracts have also been investigated as possible lead sources for pharmacological MDM2 inhibitors, in addition to particular molecules. The goal of this review is to provide a comprehensive analysis of natural MDM2 inhibitors, including their pharmacokinetic properties, binding mechanisms, and challenges in their development. Possible methods to enhance their effectiveness and therapeutic applications are also explored.

Gastrointestinal cancers represent a major global health burden and are associated with high morbidity and mortality worldwide. Despite advances in conventional therapies, treatment outcomes remain limited due to therapy resistance, toxicity, and poor long-term efficacy, highlighting the need for novel and complementary therapeutic strategies. Magnolol, a biphenolic lignan isolated from Magnolia officinalis, has attracted considerable attention due to its reported anticancer activity in multiple gastrointestinal malignancies. This review systematically summarizes current preclinical evidence on the anticancer effects of magnolol in oral, esophageal, gastric, colorectal, pancreatic, and liver cancers. Available studies demonstrate that magnolol inhibits cancer cell proliferation, migration, invasion, angiogenesis, and epithelial-mesenchymal transition, while inducing cell cycle arrest and apoptosis. These effects are mediated through modulation of key cancer-associated signaling pathways, including PI3K/Akt/NF-κB, MAPK/JNK, ERK, TGF-β/Smad, and caspase-dependent apoptotic pathways. The review further highlights recent insights into the structure-activity relationship of magnolol and its semi-synthetic derivatives, emphasizing how targeted chemical modifications influence anticancer potency and mechanistic specificity. In addition, challenges related to magnolol's poor aqueous solubility, rapid metabolism, and limited bioavailability are discussed, with particular focus on nanotechnology-based delivery systems developed to improve its pharmacokinetic profile and therapeutic performance. This current review provides an integrated overview of magnolol's molecular mechanisms, chemical optimization strategies, and translational limitations in gastrointestinal cancer therapy, and outlines future research directions necessary to support its progression toward clinical application.

The identification and detection of clinically meaningful cancer biomarkers are at the core of precision oncology development, with the potential to revolutionize cancer screening, diagnosis, prognosis, and targeted therapeutic approaches. The shifting paradigm of cancer biomarker discovery, including both new opportunities and old challenges preventing clinical translation, will be the subject of this chapter. Biomarkers such as genetic mutation, epigenetic alteration, protein expression profiling, and metabolomic fingerprints play a central role in stratifying cancer patients, predicting treatment efficacy, and monitoring disease progression. Advances in technologies at breakneck pace NGS, single-cell omics, proteomics, and artificial intelligence (AI)-driven analytics have significantly boosted the capacity to decode tumor heterogeneity, clonal evolution, and microenvironment interactions. Of particular interest, liquid biopsy platforms that focus on circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and microRNAs are transforming non-invasive diagnostics with the potential for early detection and real-time monitoring of disease. Bringing candidate biomarkers to fully validated clinical tests, however, is an elusive goal. The current chapter critically assesses barriers like biological heterogeneity, lack of adequate assay standardization, sparse longitudinal validation, and variability in data interpretation across different platforms and populations. Tumor plasticity and pressure from therapy-induced dynamic alterations further cloud biomarker dependability, necessitating adaptive and integrative solutions. Consistently, there is a growing shift away from single-marker solutions toward composite biomarker panels guided by multi-omics integration and AI-guided predictive modeling. The chapter will also address current clinical applications of established biomarkers such as HER2 in breast cancer, EGFR in lung cancer, and PD-L1 expression and tumor mutational burden (TMB) in cancer immunotherapy and the limitations these biomarkers have in heterogeneous populations. Further, the ethical and regulatory considerations of biomarker development including data privacy issues in AI-based applications, equitable access to advanced diagnostics in low-resource settings, and cost-effectiveness for roll-out at scale will be addressed. Directions of the future will include developing standardized validation pipelines, interdisciplinarity, and biomarker platforms available globally that can be dynamically calibrated based on patient-specific profiles. Finally, this chapter hopes to set an all-encompassing road map toward closing the gap between the discovery of molecular biomarkers and clinical application in the hope of fashioning a better more accurate, individualized, and equitable future in cancer treatment.

Biomarkers in cancer are diverse molecular, cellular, or biochemical indicators that help diagnose, predict, and treat various cancers. They can be detected in tissues, blood, or other bodily fluids and guide personalized treatment strategies. Biomarkers are an integral component in oncology. They are described as prognostic, predictive, and diagnostic based on their applicability. Apart from molecular markers such as protein expression, other advanced biomarkers are being developed: circulating tumor cells (CTCs) and lipid metabolism-related markers. Continuous advances in molecular profiling, liquid biopsy, and computational analysis promise to enhance the utility of biomarkers in personalized oncology. In addition, high-throughput techniques (next-generation sequencing, mass spectrometry, and immune cell profiling) are being utilized for biomarker discoveries to support personalized therapeutics in oncology. The future of biomarkers lies in more advanced tools such as radiogenomics and artificial intelligence, which will cater to the requirement of more precise biomarkers. Artificial intelligence is revolutionizing the biomarkers by analyzing large data sets in short stipulated time. In the present chapter, we delve into the utility, advancement, and challenges of biomarkers in oncology.

Background Viral infections can increase the likelihood of an individual developing membranous nephropathy (MN). Limited information is available regarding the treatment approaches for such cases. We conducted a review focusing on hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency virus (HIV)-associated MN. Materials and Methods Our investigation encompassed patient records and cases documented in the literature, utilizing various search engines (PubMed, Scopus, Embase, and Web of Science). We aimed to identify all reported instances of MN associated with HBV, HCV, or HIV infections between 2010 and February 2023 in individuals aged 18 years and above, who underwent PLA2R testing in their serum or kidney biopsy. Results We analyzed 63 patients with MN associated with viral infections, comprising 7 patients from our center and 57 from the review, consisting of 43% with HIV, 28.5% with HBV, 17.5% with HCV, and 11% with mixed infections. The average age of these patients was 47 years. Their mean proteinuria, serum albumin, and creatinine levels were 7.5 g/day, 2.3 g/dl, and 1.4 mg/dl, respectively. Two-thirds of these cases were PLA2R-related. Notably, 24% of patients achieved remission solely through antiviral treatment, while nearly 40% attained remission with a combination of antiviral and immunosuppression therapies. Eight patients did not achieve remission despite receiving immunosuppressive therapy and antiviral agents. Conclusion The review suggests that using antiviral medications alone or combined with immunosuppressive therapy can lead to substantial remission in patients with viral-associated MN.

There is evidence to suggest that M-type phospholipase A2 (PLA2R) antibodies activate the mannose-binding lectin (MBL) cascade, resulting in glomerular damage and proteinuria in patients with primary membranous nephropathy (PMN). Furthermore, there are few reports indicating that aberrant MBL activation is associated with endothelial dysfunction and accelerated atherosclerosis. While PMN is a common cause of adult nephrotic syndrome, and patients are at increased risk of cardiovascular disease (CVD), there is a lack of research that explores the factors that contribute to this condition. This study aims to determine the MBL levels in PMN and their relation to the clinical activity and endothelial dysfunction in PMN. The MBL levels of 22 biopsy-confirmed PMN patients were assessed at baseline and after 6 months of immunosuppressive therapy. In order to evaluate endothelial dysfunction in PMN patients, flow-mediated vasodilation (FMD) was measured at baseline and after treatment. A total of 22 healthy controls were included in this study to measure MBL levels and FMD. A significant difference was observed between MBL levels in PMN patients and healthy controls (p < .01). MBL levels decreased significantly after immunosuppressive therapy (p = .04). The baseline MBL levels and FMD levels exhibited a strong correlation (Spearman correlation coefficient [rho] = 0.51: p = .01). In conclusion, the study signals the activation of the MBL cascade and its association with endothelial dysfunction in PMN patients. image

Gastrointestinal cancer is a malignant condition of the gastrointestinal tract (GI) which affect multi-organs of digestive system, such as esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum, and anus. Gastrointestinal cancer is a 5th most common malignant cancer and 4th major cause in cancer-related mortality rate. Various significant facilities are available that have reduced the radio-resistance, chemo-resistance, and their adverse side effects. However, there are serious side effects associated with chemical and radiations during the process. Baicalein is a natural flavonoid extracted from dried roots of Scutellaria baicalensis, showing anti-cancerous property. It is also participating in inhibiting metastasis, accelerating apoptosis and elevating autophagy through inhibition of inflammation and cell proliferation. In this review, we have focused on Chemistry and pharmacokinetics of Baicalein for drug designing and clinical applications majorly in gastrointestinal cancer. Moreover, various types of cancer related to gastrointestinal, role of nanotechnology, and its synergism for reducing cancer are also discussed. Thus, the review would be beneficial to explore the role of baicalein against gastrointestinal cancer treatment.

Primary membranous nephropathy (PMN), an autoimmune disease, is the most common cause of nephrotic syndrome in middle-aged non-diabetic adults. PMN pathophysiology includes Th1/Th2 paradigm. The IL-23/IL-17 pathway is implicated in autoimmune kidney disorders, but no study has examined its relationship with PMN. In several unrelated studies, PMN patients reported to have paradoxical IL-17 levels. This manuscript describes the best possible association of IL-23/IL-17 axis with PMN. Biopsy-proven PMN patients and age, gender-matched healthy controls were enrolled. Serum-PLA2R (Euroimmune, Germany), IL-23 and IL-17 (R&D; USA), was measured using ELISA along with biochemical parameters. Appropriate statistical tools were used for analysis. One hundred eighty-nine PMN patients (mean age 41.70 ± 12.53 years) and 100 controls (mean age 43.92 ± 10.93 years) were identified. One hundred forty were PLA2R-related. PMN patients had median proteinuria, serum albumin, and creatinine of 6.12 (3.875, 9.23) g/day, 2.32 (1.96, 2.9) g/dl, and 0.89 (0.7, 1.1) mg/dl, respectively. IL-17, but not IL-23, was significantly increased in PMN patients compared to controls (IL-17, median: 12.07 pg/ml (9.75, 24.56) vs median: 9.75 pg/ml (8.23, 17.03) p = 0.0002); (IL23, median: 6.04 pg/ml (4.22, 10.82) vs median: 5.46 pg/ml (3.34, 9.96) p = 0.142). IL-17 and IL-23 correlated significantly ( p 0.05) in PMN patients, and similar trend was seen when grouped into PLA2R-related and -unrelated groups. The levels of IL-23 ( p = 0.057) and IL-17 ( p = 0.004) were high in MN patients that did not respond to the treatment. The current finding may indicate or suggest the involvement of IL-23/IL-17 PMN pathogenesis. A comprehensive investigation is needed to evaluate IL-23/IL-17 axis with renal infiltrating immune cells, and external stimuli.

Primary membranous nephropathy (PMN) is an autoimmune disorder and a leading cause of nephrotic syndrome in adults. Phospholipase A2 receptor (PLA2R) is the commonest antigen against which circulating antibodies are formed in PMN. It is evident that PLA2R activates the MBL cascade resulting in glomerular damage and proteinuria. However, there are few reports which indicate association of aberrant MBL activation with endothelial dysfunction and accelerated atherosclerosis. Despite PMN being a common cause of adult nephrotic syndrome, there is a lack of studies on cardiovascular outcomes in PMN

Dysregulation of epigenetic mechanisms have been depicted in several pathological consequence such as cancer. Different modes of epigenetic regulation (DNA methylation (hypomethylation or hypermethylation of promotor), histone modifications, abnormal expression of microRNAs (miRNAs), long non-coding RNAs, and small nucleolar RNAs), are discovered. Particularly, lncRNAs are known to exert pivot roles in different types of cancer including breast cancer. LncRNAs with oncogenic and tumour suppressive potential are reported. Differentially expressed lncRNAs contribute a remarkable role in the development of primary and acquired resistance for radiotherapy, endocrine therapy, immunotherapy, and targeted therapy. A wide range of molecular subtype specific lncRNAs have been assessed in breast cancer research. A number of studies have also shown that lncRNAs may be clinically used as non-invasive diagnostic biomarkers for early detection of breast cancer. Such molecular biomarkers have also been found in cancer stem cells of breast tumours. The objectives of the present review are to summarize the important roles of oncogenic and tumour suppressive lncRNAs for the early diagnosis of breast cancer, metastatic potential, and chemotherapy resistance across the molecular subtypes.

Background and Aim: Primary glomerular disease accounts for one-sixth of all chronic kidney diseases (CKDs) in India. We remain limited in our ability to effectively treat these conditions because of lack of understanding of the disease mechanisms and lack of predictors to identify the clinical course and therapeutic responsiveness. We propose to develop a network of investigators in glomerular diseases, collect information in a systematic fashion to understand the clinical outcomes, answer translational research questions better, and identify and recruit patients for clinical trials. Materials and Methods: This is a prospective, observational study. The Indian TrANslational GlomerulonephrItis BioLogy nEtwork (I-TANGIBLE) cohort will enroll patients (>18 years) with biopsy-proven minimal change disease (MCD), focal segmental glomerulonephritis (FSGS), membranous nephropathy (MN), IgA nephropathy (IgAN), or membranoproliferative glomerulonephritis (MPGN) (immune complex- and complement-mediated), with first biopsy taken within 2 years of enrollment. Patients with estimated glomerular filtration (eGFR) rate <15 ml/min/1.73 m 2 for >3 months at the time of screening, kidney transplant or bone marrow transplant recipients, patients with active malignancy, and patients with active hepatitis B/C replication or human immunodeficiency virus (HIV)-I/II will be excluded. Clinical details including history, medication history and details, and family history will be obtained. Consenting patient’s blood and urine samples will be collected and stored, aligned to their clinical follow-up. Expected Outcomes: The network will allow accurate ascertainment of disease burden of glomerular diseases across study sites, establishment of the treatment pattern of common glomerular diseases, investigation of medium- and long-term outcomes (remission, relapse, rate of eGFR decline), and building a suitable infrastructure to carry out clinical trials in primary glomerular disease.

The Kidney Disease Improving Global Outcomes guidelines recommend incorporating anti-M-type Phospholipase A2 receptor (PLA2R) antibody titers in steering treatment decisions for patients with primary membranous nephropathy (PMN).1