Abhijit G. Banerjee

Leukotriene B4 (LTB4), the terminal product of the 5-lipoxygenase (5-LO)/leukotriene A4 hydrolase (LTA4H) pathway, is one of the most potent neutrophil chemoattractants in human biology. Three decades of lesional-skin and leukocyte studies have established LTB4 as a mechanistically central, if therapeutically underexploited, mediator in both psoriasis and atopic dermatitis (AD); two diseases with opposing T-helper polarization but convergent neutrophilic and pruritic phenotypes. Literature searches conducted in PubMed, Scopus, Web of Science, Embase, and the Cochrane Library identified 642 records. After removal of 138 duplicate or otherwise ineligible records, 504 records underwent title and abstract screening. A total of 71 full-text reports were assessed for eligibility, of which 49 were excluded for predefined reasons. Twenty-two studies fulfilled the inclusion criteria and were included in the qualitative synthesis. This review thus synthesizes the biochemical basis of cutaneous LTB4 generation, the direct evidence for its role in psoriatic plaque formation and AD flares, receptor-level findings in both conditions, and the therapeutic trials of antileukotriene agents in dermatology. We conclude by outlining unresolved questions relevant to LTA4H as a rate-limiting, druggable node shared across two clinically distinct but biochemically overlapping disorders.

Angiogenesis is central to tumor development and metastasis as it facilitates oxygen and nutrient supplies to cancer cells. The inhibition of angiogenic pathways is a commonly used strategy in the treatment of cancer, usually through inhibitory actions that first lead to the targeted suppression of the key pro‑angiogenic factor, vascular endothelial growth factor (VEGF), and its upstream regulator, hypoxia‑inducible factor 1α (HIF‑1α). Emodin, a common anthraquinone derivative of natural origins, has a variety of actions to inhibit angiogenesis, which include the ability to inhibit the expression of VEGF, as well as the ability to reverse the stabilization of HIF‑1α and inhibit tumor microvessel branching. Moreover, emodin is recognized for pathways other than those involving VEGF, such as fibroblast growth factor and platelet‑derived growth factor, which affect endothelial cell proliferation and pericyte recruitment. Emodin can facilitate vessel destabilization by acting on several angiopoietins, leading to the disruption of the function of the tumor vasculature. These mechanisms collectively obstruct tumor vascularization, deprive tumor cells of vital nutrients and prevent cancer progression. In silico molecular docking analyses suggest that emodin may interact with the ATP‑binding pocket of VEGFR‑2 and the oxygen‑dependent degradation domain of HIF‑1α. Although these findings support a plausible multi‑target inhibitory profile for emodin, direct biochemical and structural validation of these interactions remains limited. Pre‑clinical studies to date have determined it to be a critical anti‑angiogenic agent and a synergistic agent in combination with chemotherapy and/or targeted therapies that can be administered to patients. Future studies are required to address bioavailability issues, target the associated resistance mechanisms, and explore mechanisms with which to increase its efficacy as an adjuvant in the treatment of cancer.

Background: Swertiamarin, a secoiridoid glycoside from Swertia chirayita, is a principal bitter constituent implicated in the plant's antidiabetic, hepatoprotective, anti-inflammatory, and chemopreventive properties, yet its polypharmacological profile has not been systematically synthesized for translational drug discovery purposes.

Salivary exosomes have emerged as a promising non-invasive liquid biopsy platform for the detection of both localized and distant malignancies. Tumour-derived exosomes originating from systemic cancers can enter systemic circulation, interact with salivary gland epithelial cells, and subsequently release tumour-associated nucleic acids and proteins into saliva. Recent studies have demonstrated that salivary exosomal miRNAs, mRNAs and proteins possess significant diagnostic potential for early-stage tumour detection, particularly in pancreatic cancer, lung cancer and oral squamous cell carcinoma (OSCC). Pilot studies in pancreatobiliary cancers identified elevated salivary exosomal miR-1246 and miR-4644 with combined diagnostic area under the curve (AUC) values of 0.833, whereas meta-analyses of saliva-derived miRNAs reported pooled sensitivity and specificity values of 87% and 86%, respectively, with pooled AUCs approaching 0.93. Lung cancer-associated salivary exosomal biomarkers including BPIFA1, CRNN, MUC5B and IQGAP1, together with mRNA panels comprising CCNI, EGFR, FGF19, GREB1 and FRS2, demonstrated high discriminatory accuracy for early-stage disease. In OSCC, salivary exosomal miRNAs including miR-21, miR-31, miR-155 and miR-200c consistently demonstrated AUC values exceeding ~0.89. Emerging biomarkers such as miR-10b-5p and miR-486-5p also exhibit promising diagnostic and therapeutic relevance in head and neck squamous cell carcinoma (HNSCC). Despite encouraging proof-of-concept evidence, substantial challenges remain, including lack of methodological standardization, limited cohort sizes, absence of population-scale prevalence studies and interstudy heterogeneity. Future translational advancement will require multicentre prospective validation studies integrating multi-omics biomarker panels and direct comparison with blood-based liquid biopsy approaches.

Carnosol, a Coffea arabica phenolic diterpene, has attracted attention as a multi-target anticancer compound. In cervical cancer models, it appears to regulate cancer-related gene expression, suppress proliferation, promote apoptosis, and reduce invasion-related behavior. Supporting evidence from other tumor systems shows effects on major oncogenic pathways, including NF-κB, MAPK/ERK, p38, PI3K/AKT/mTOR, p53/MDM2, and Nrf2. However, the current evidence remains preclinical, and clinical benefit in metastatic cervical cancer has not been established.

Emodin is a naturally occurring anthraquinone being investigated for its anticancer potential due to its ability to modulate the cell cycle and inhibit tumor progression. The cell cycle is composed of a series of events that dictate cell growth and cell division. The G0/G1 checkpoint is the resting stage before the first gap phase (G1), whereas the G2/M checkpoint is the working stage from the second gap phase (G2) before mitosis begins. Emodin exerts its effects by the following means: Cyclins, which propel the cells through the cell cycle stages; cyclin-dependent kinases (CDKs), which are energy sources that, along with cyclins, push the cell cycle further; and finally, CDK inhibitors, such as p21 and p27, which can inhibit CDK activity. G0/G1 arrest is mediated by the suppression of cyclin D/CDK4 and cyclin E/CDK2 activity, whereas G2/M arrest results from the inhibition of cyclin B/CDK1 and the disruption of mitotic progression. G2/M arrest is further reinforced by the activation of the checkpoint kinases, Chk1 and Chk2. These kinases operate downstream of DNA damage sensors and effectors to maintain cell cycle blockade. The present review discusses the mechanisms of emodin-induced cell cycle arrest. In preclinical settings, emodin has been shown to be capable of suppressing tumor cell proliferation in multiple cancer models, both by itself and in combination with standard chemotherapy or radiotherapy. However, suboptimal bioavailability and metabolic instability are obstacles that have hindered its clinical application, with results being inconsistent among cancer types. Future studies are required to develop more efficacious drug delivery systems, identify predictive biomarkers and conduct strong clinical trials. Addressing these issues may position emodin as a viable cancer therapeutic option, either alone or in combination with current therapies.

Cajanus cajan (pigeon pea) is a nutritionally and medicinally important legume that has emerged as a rich source of bioactive stilbenoids, flavonoids, and phenolic compounds with diverse pharmacological properties. Phytochemical investigations have identified several biologically active constituents, including cajaninstilbene acid, cajanol, pinostrobin, orientin, vitexin, quercetin derivatives, and numerous novel stilbenoids exhibiting antioxidant, anti-inflammatory, antimicrobial, antidiabetic, anticancer, neuroprotective, and hepatoprotective activities. Early ecological studies demonstrated that phenolic compounds present on pigeon pea pod surfaces influence insect feeding behavior, suggesting an intrinsic defense role of these metabolites. Subsequent pharmacological studies revealed modulation of oxidative stress, inflammatory signaling, glucose metabolism, apoptosis, and cellular survival pathways.

Angiogenesis is central to tumor development and metastasis because it facilitates oxygen and nutrient supplies to cancer cells. Inhibiting angiogenic pathways is a commonly used strategy in the treatment of cancer, usually through inhibitory actions that first determine targeted apoptosis of the key proangiogenic factor, vascular endothelial growth factor (VEGF), and its upstream regulator, hypoxia-inducible factor 1-alpha (HIF-1α). Emodin, a common anthraquinone derivative of natural origins, has a variety of actions to inhibit angiogenesis, which include the ability to inhibit the expression of VEGF, as well as the ability to reverse stabilization of HIF-1α and inhibit tumor microvessel branching. Moreover, emodin is recognized for pathways other than those involving VEGF, such as fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF), which impact endothelial cell proliferation and pericyte recruitment. Emodin can facilitate vessel destabilization by acting on several angiopoietins, causing the function of the tumor vasculature to be disrupted. Molecular docking studies have shown emodin can bind the ATP-binding pocket of VEGFR-2 and the degradation domain of HIF-1α, acting as a multi-target inhibitory compound. These mechanisms collectively obstruct tumor vascularization, deprive tumor cells of vital nutrients, and prevent cancer progression. Pre-clinical studies to date have determined it to be a significant anti-angiogenic agent and a synergistic agent in combination with chemotherapy and/or targeted therapies that can be given to patients. Future studies will address bioavailability issues, target the associated resistance mechanisms, and explore ways to increase its efficacy as an adjuvant in cancer treatment.

Background: Glycosaminoglycans (GAGs) and proteoglycans (PGs) are pivotal extracellular matrix (ECM) components dysregulated in oral squamous cell carcinoma (OSCC), contributing to tumor stiffness, invasion, and therapeutic resistance through altered sulfation and mechanobiology. Methods: This narrative review synthesizes structural, distributional, diagnostic, prognostic, and therapeutic aspects of GAGs/PGs in normal versus malignant oral tissues, incorporating mechanobiological roles and emerging SUMO-1 inhibition strategies. Results: Normal oral tissues feature DS-dominant GAGs (60%) and PGs like versican/decorin for matrix organization, while OSCC shows doubled GAG content, hypersulfation (↑CS-4S/6S, HS 6-O-S), and overexpressed agrin/perlecan, stiffening ECM via PG hydration, collagen crosslinking, and YAP/TAZ activation. Serum HA elevation (153 vs. 104 ng/ml; p<0.05) aids monitoring; sulfation profiling promises diagnostics (pan-cancer AUC 0.74-0.98). Prognostically, CS total and low tissue HA predict poor survival. Therapeutically, sulfotransferase/ sulfatase modulation, GAG mimetics (G2C), and ginkgolic acid (GA; 5-10 μM inhibits EMT via SMAD4 desumoylation) reduce invasion (40-60%) and xenograft growth. Conclusions: GAG/PG hypersulfation and mechanobiology drive OSCC progression, offering biomarker and therapeutic targets. Prospective trials validating sulfation/ GA combinations are warranted to enhance precision oncology.

Fusobacterium nucleatum has emerged as a key microbial contributor to colorectal cancer (CRC) progression through immune modulation and tumor colonization. Its outer membrane adhesin Fap2 functions as a bifunctional lectin that recognizes tumor-associated glycans and engages immune inhibitory receptors. Recent structural insights reveal a unique β-helical architecture enabling simultaneous binding to Gal-GalNAc moieties on tumor cells and TIGIT on immune cells. This dual interaction underpins bacterial tropism to CRC and facilitates immune evasion. Here, we synthesize structural, functional, and translational insights into Fap2 biology, highlighting therapeutic strategies targeting the Fap2–TIGIT axis and identifying gaps in small-molecule inhibition, particularly from natural products.