Cancer is, globally, one of the main causes of death. Even though various therapies are available, they are still painful because of their adverse side effects. Available treatments frequently fail due to unpromising responses, resistance to classical anticancer drugs, radiation therapy, chemotherapy, and low accessibility to tumor tissues. Developing novel strategies to minimize adverse side effects, improve chemotherapy sensitivity, and control cancer progression is needed. Many studies have suggested small dietary molecules as complementary treatments for cancer patients. Different components of herbal/edible plants, known as flavonoids, have recently garnered attention due to their broad biological properties (e.g., antioxidant, antiviral, antimicrobial, anti-inflammatory, anti-mutagenic, anticancer, hepatoprotective, and cardioprotective). These flavonoids have shown anticancer activity by affecting different signaling cascades. This article summarizes the key progress made in this area and discusses the role of flavonoids by specifically inhibiting the PI3K/Akt/mTOR pathway in various cancers.

Natural products play a critical role in the discovery and development of numerous drugs for the treatment of various types of cancer. These phytochemicals have demonstrated anti-carcinogenic properties by interfering with the initiation, development, and progression of cancer through altering various mechanisms such as cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. Treating multifactorial diseases, such as cancer with agents targeting a single target, might lead to limited success and, in many cases, unsatisfactory outcomes. Various epidemiological studies have shown that the steady consumption of fruits and vegetables is intensely associated with a reduced risk of cancer. Since ancient period, plants, herbs, and other natural products have been used as healing agents. Likewise, most of the medicinal ingredients accessible today are originated from the natural resources. Regardless of achievements, developing bioactive compounds and drugs from natural products has remained challenging, in part because of the problem associated with large-scale sequestration and mechanistic understanding. With significant progress in the landscape of cancer therapy and the rising use of cutting-edge technologies, we may have come to a crossroads to review approaches to identify the potential natural products and investigate their therapeutic efficacy. In the present review, we summarize the recent developments in natural products-based cancer research and its application in generating novel systemic strategies with a focus on underlying molecular mechanisms in solid cancer.

Despite decades of research, there is no specific therapy for acute pancreatitis (AP). In the current study, we have evaluated the efficacy of pirfenidone, an antiinflammatory and antifibrotic agent that is approved by the FDA for treatment of idiopathic pulmonary fibrosis (IPF), in ameliorating local and systemic injury in AP. Our results suggest that treatment with pirfenidone in therapeutic settings (e.g., after initiation of injury), even when administered at the peak of injury, reduces severity of local and systemic injury and inflammation in multiple models of AP. In vitro evaluation suggests that pirfenidone decreases cytokine release from acini and macrophages and disrupts acinar-macrophage crosstalk. Therapeutic pirfenidone treatment increases IL-10 secretion from macrophages preceding changes in histology and modulates the immune phenotype of inflammatory cells with decreased levels of inflammatory cytokines. Antibody-mediated IL-10 depletion, use of IL-10–KO mice, and macrophage depletion experiments confirmed the role of IL-10 and macrophages in its mechanism of action, as pirfenidone was unable to reduce severity of AP in these scenarios. Since pirfenidone is FDA approved for IPF, a trial evaluating the efficacy of pirfenidone in patients with moderate to severe AP can be initiated expeditiously.

An outbreak of coronavirus disease 2019 (COVID-19) emerged in China in December 2019 and spread so rapidly all around the globe. It’s continued and spreading more dangerously in India and Brazil with higher mortality rate. Understanding of the pathophysiology of COVID-19 depends on unraveling of interactional mechanism of SARS-CoV-2 and human immune response. The immune response is a complex process, which can be better understood by understanding the immunological response and pathological mechanisms of COVID-19, which will provide new treatments, increase treatment efficacy, and decrease mortality associated with the disease. In this review we present a amalgamate viewpoint based on the current available knowledge on COVID-19 which includes entry of the virus and multiplication of virus, its pathological effects on the cellular level, immunological reaction, systemic and organ presentation. T cells play a crucial role in controlling and clearing viral infections. Several studies have now shown that the severity of the COVID-19 disease is inversely correlated with the magnitude of the T cell response. Understanding SARS-CoV-2 T cell responses is of high interest because T cells are attractive vaccine targets and could help reduce COVID-19 severity. Even though there is a significant amount of literature regarding SARS-CoV-2, there are still very few studies focused on understanding the T cell response to this novel virus. Nevertheless, a majority of these studies focused on peripheral blood CD4+ and CD8+ T cells that were specific for viruses. The focus of this review is on different subtypes of T cell responses in COVID-19 patients, Th17, follicular helper T (TFH), regulatory T (Treg) cells, and less classical, invariant T cell populations, such as δγ T cells and mucosal-associated invariant T (MAIT) cells etc that could influence disease outcome.

Cytotoxicity and IFN- secretion along with surface markers such as NKG2D drives the dysregulation of M2 macrophages, facilitating the upregulation of macrophages in PV. However, macrophage interplay with NK cells through the NKG2D-MICA/B axis promoted M1 polarization while impairing the M2 state. Additionally, NKG2D blockade revealed partial reversal of the inflammatory state, suggesting an active role of NKG2D and involvement of other contributors in this axis. Modulation of signaling pathways, such as those involved in keratinocytes and cellular cross-talks as seen in vulgaris, provides promising approaches for future therapeutics.Targeting multicellular networks involved in pathogenesis may offer superior and effective therapeutics compared to singular targeting.Vitiligo is another skin condition that is considered an autoimmune depigmentary disease where melanocytes are selectively destroyed by cytotoxic CD8 + T cells due to a deficiency of regulatory T cells (Tembhre and Khan; Tembhre et al.; Sharma et al.). Luo et al. described the advancement in the vitiligo treatment from the conventional immunosuppressants (e.g., corticosteroids and phototherapy) to next-generation targeted immunotherapies, where JAK inhibitors (e.g., ruxolitinib) were FDA approved for vitiligo in 2022 for topical use, whereas other oral JAK inhibitors (e.g., tofacitinib, baricitinib, upadacitinib) are undergoing trials for nonsegmental active vitiligo. Further, systemic sclerosis (SSc) is a chronic autoimmune disease characterized by marked vasculopathy and tissue fibrosis. Liu M. described that the advancement of multi-omics techniques like single-cell, spatial transcriptomics, RNA sequencing, and proteomics has revealed various cell-specific therapeutic targets in various human diseases, including SSc. As a consequence of this, there is a paradigm shift in the treatment strategies that is more inclined towards targeted immunotherapies instead of generalized immunosuppression offered by conventional therapies. The emerging therapies include B-cell depletion (rituximab, belimumab), T-cell inhibition (abatacept), multi-cytokine targeting JAK inhibitors (e.g., tofacitinib, baricitinib), IL-6 inhibition (tocilizumab), and cell-based therapies (e.g., autologous and allogeneic CD19 CAR T cells). Immunotherapies may be instrumental in the treatment of autoimmune diseases like vitiligo and SSc treatment provided identification of candidate immune biomarkers that may directly drive the disease pathogenesis.The role of neutrophil, particularly neutrophil extracellular traps (NETs), has garnered significant attention in the past two decades, and its role has been implicated in various autoimmune and inflammatory diseases, including psoriasis (Ojha et al.). Presence of NETotic neutrophils has been reported in lesional epidermis (Munro's microabscesses) and dermis of psoriasis. The NETs armamentarium consists of potent inflammatory components like myeloperoxidases (MPO), neutrophil elastase (NE), proteinase 3 (PR3), cathepsin, LL-37, and βdefensin that can exacerbate the disease activity, leading to episodic appearance of disease flares.Tang et al. reported promising therapeutics against the NETs-derived components like NE, MPO, PAD4 (Peptidyl arginine deiminase 4, a key enzyme in NETosis), deoxyribonucleic acid (e.g., DNase I), and reactive oxygen species (ROS), where ROS scavengers (N-acetylcysteine (NAC), MitoTempo, ethyl pyruvate, diphenyleneiodonium, etc.) may play a significant role in neutrophildriven dermatoses.Over the past decade, the selective targeting of the IL-23 p19 subunit has emerged as one of the most significant developments in reshaping psoriasis treatments. A meta-analysis by Ashraf et al. presents the first comprehensive evaluation of mirikizumab (LY3074828) by pooling data from three randomized controlled trials involving 1,752 participants and demonstrating significant improvements in skin clearance rates compared with placebo. Importantly, therapeutic benefits extended beyond skin clearance to include nail disease, palmoplantar involvement, quality-of-life measures, and overall disease burden. Also, there were no significant differences in serious adverse events between groups, which supports the mechanistic rationale for selective p19 blockade over broader cytokine inhibition. Taken together, these findings suggest that mirikizumab is an effective IL-23 inhibitor, but with some limitations, including the lack of long-term data and head-to-head comparisons with established biologics, which were excluded from this meta-analysis. reported the first systematic transcriptomic meta-analysis in primary lymphocytic scarring alopecias, integrating six batch-corrected datasets from 134 patients across frontal fibrosing alopecia (FFA), lichen planopilaris (LPP), and central centrifugal cicatricial alopecia (CCCA), and 49 healthy controls. The three subtypes converge on a shared IFN-γ-driven inflammatory core but diverge considerably beyond it. FFA and LPP show pronounced JAK-STAT enrichment, with partial reversal achievable using brepocitinib. CCCA follows a different course, such as mitochondrial dysfunction, dominating epigenetic repression, and inhibition of the JAK pathway, as have a lower effect. This clear clinical distinction reveals that CCCA may require metabolically targeted intervention rather than the anti-inflammatory approaches effective in FFA and LPP.Importantly, downregulated gene sets enriched for cardiometabolic traits were observed across all three subtypes, suggesting that chronic scalp inflammation may have systemic consequences warranting closer comorbidity screening. In conclusion, endotype-based treatment selection is increasingly supported by direct evidence rather than theoretical rationale. Fibrosis continues to represent the principal barrier to recovery in both systemic sclerosis and scarring alopecia, and the repeated failure of anti-inflammatory therapy...