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Oral cancer is one of the leading causes of cancer-related deaths, and it has become a matter of serious concern due to the alarming rise in its incidence rate worldwide. Despite recent advancements in oral cancer treatment strategies, there are no significant improvements in patient's survival rate. Among the numerous cell signaling pathways involved in oral cancer development and progression, STAT3 is known to play a multifaceted oncogenic role in shaping the tumor pathophysiology. STAT3 hyperactivation in oral cancer contributes to survival, proliferation, invasion, epithelial to mesenchymal transition, metastasis, immunosuppression, chemoresistance, and poor prognosis. A plethora of pre-clinical and clinical studies have documented the role of STAT3 in the initiation and development of oral cancer and showed that STAT3 inhibition holds significant potential in the prevention and treatment of this cancer. However, to date, targeting STAT3 activation mainly involves inhibiting the upstream signaling molecules such as JAK and IL-6 receptors. The major challenge in targeting STAT3 lies in the complexity of its phosphorylation- and dimerization-independent functions, which are not affected by disrupting the upstream regulators. The present review delineates the significance of the STAT3 pathway in regulating various hallmarks of oral cancer. In addition, it highlights the STAT3 inhibitors identified to date through various preclinical and clinical studies that can be employed for the therapeutic intervention in oral cancer treatment.

The medicinal plant Scutellaria baicalensis, commonly known as Chinese skullcap or Huang-Qin, has been used as a traditional medicine for several thousand years. The roots of this plant contain bioactive compounds, such as wogonin (WOG), wogonoside, baicalein, and baicalin. The aim of this article is to evaluate the therapeutic potential and mechanisms of action of WOG against different cancers. Numerous in vitro and in vivo studies have revealed that WOG exerts immense therapeutic potential against bladder cancer, breast cancer, cholangiocarcinoma, cervical cancer, colorectal cancer, gallbladder cancer, gastric cancer, glioblastoma, head and neck cancer, hepatic cancer, leukemia, lung cancer, lymphoma, melanoma, multiple myeloma, neuroblastoma, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, and renal cancer by regulating various cell signaling pathways. WOG, in combination with established chemotherapeutic drugs, improves the efficacy of treatment and lowers toxicity. Nevertheless, human trials are warranted to validate these findings. Numerous preclinical studies, combined with an extensive margin of safety and no severe side effects, underscore WOG's therapeutic potential as an anticancer drug. These studies propound the use of WOG as a potential anticancer candidate; however, further high-quality studies are required to firmly establish the clinical efficacy of WOG for the prevention and treatment of human malignancies.

In recent years, triple-negative breast cancer (TNBC) has emerged as the most aggressive subtype of breast cancer and is usually associated with increased mortality worldwide. The severity of TNBC is primarily observed in younger women, with cases ranging from approximately 12%-24% of all breast cancer cases. The existing hormonal therapies offer limited clinical solutions in completely circumventing the TNBC, with chemoresistance and tumor recurrences being the common hurdles in the path of TNBC treatment. Accumulating evidence has correlated the dysregulation of long noncoding RNAs (lncRNAs) with increased cell proliferation, invasion, migration, tumor growth, chemoresistance, and decreased apoptosis in TNBC. Various clinical studies have revealed that aberrant expression of lncRNAs in TNBC tissues is associated with poor prognosis, lower overall survival, and disease-free survival. Due to these specific characteristics, lncRNAs have emerged as novel diagnostic and prognostic biomarkers for TNBC treatment. However, the underlying mechanism through which lncRNAs perform their actions remains unclear, and extensive research is being carried out to reveal it. Therefore, understanding of mechanisms regulating the modulation of lncRNAs will be a substantial breakthrough in effective treatment therapies for TNBC. This review highlights the association of several lncRNAs in TNBC progression and treatment, along with their possible functions and mechanisms.

The present study describes an outbreak of Classical swine fever (CSF) in an organized pig farm followed by an episode of CSF virus (CSFV) associated congenital tremors in piglets. The outbreak was recorded in a newly procured herd of Hampshire pigs housed adjacent to the existing pigs of the farm. The recorded CSF outbreak caused a mortality of 100% in the newly procured and 54.28% in the existing herd. As the disease subsides, the clinically recovered boars were served naturally with Tamworth gilts. Though, the sows farrowed on usual gestation period, litters born to each sow showed congenital tremors and eventually died within 24 h of birth. Necropsy analysis of affected piglets was indicative of CSFV infection and was further confirmed using RT-PCR signifying a transplacental infection. The CSFV strains from the initial outbreak and post outbreak episode of congenital tremors were successfully isolated in PK-15 cells and detected in indirect FAT and RT-PCR. Phylogenetic analysis based on E2 gene and 5′NTR of CSFV grouped the isolates within the genotype 2.2 and revealed close resemblance with previously reported Indian isolates of CSFV genotype 2.2 origin. To the best of our knowledge, this is the first report of CSFV induced congenital form reported from India under natural conditions.

Chronic diseases are considered a major public health concern worldwide, and most of these diseases like cancer, cardiovascular, metabolic, and neurological disorders occur due to atypical regulation of multiple signaling pathways. It has also been observed that most of the currently approved therapies for these diseases fail to show prolonged efficacy due to their mono-targeted nature and are associated with the development of chemoresistance, thus restricting their utility. The plant-derived compounds, on the other hand, show multi-targeted nature, and thus these phytochemicals have gained wide attention as they offer negligible side effects. The present review aims to recapitulate the potential effects of one such phytochemical, Scopoletin, which was found to have a diverse range of pharmacological activities such as anti-cancer, anti-diabetic, anti-inflammatory, cardioprotective, hepatoprotective, etc. Scopoletin modulated multiple molecular signatures in cancer, including AMPK, EGFR, MAPK/ ERK, NF-κB, PI3K/Akt/ mTOR, and STAT3; regulated the levels of critical markers of metabolic diseases such as ALT, AST, TG, and TC; inflammatory diseases such as ILs and TNFs; neurological diseases such as AChE, etc. thus relieving the symptoms and severity associated with these diseases. Further, this compound has a non-toxic nature and possesses an excellent pharmacokinetic property, which warrants further investigation in clinical settings for developing it as a potential drug.

Gall bladder cancer (GBC) is a rare and one of the most aggressive types of malignancies, often associated with a poor prognosis and survival. It is a highly metastatic cancer and is often not diagnosed at the initial stages, which contributes to a poor survival rate of patients. The poor diagnosis and chemoresistance associated with the disease limit the scope of the currently available surgical and nonsurgical treatment modalities. Thus, there is a need to explore novel therapeutic targets and biomarkers that will help relieve the severity of the disease and lead to advanced therapeutic strategies. Accumulating evidence has correlated the atypical expression of various noncoding RNAs (ncRNAs), including circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and small nucleolar RNAs (snoRNA) with the increased cell proliferation, epithelial–mesenchymal transition (EMT), invasion, migration, metastasis, chemoresistance, and decreased apoptosis in GBC. Numerous reports have indicated that the dysregulated expression of ncRNAs is associated with poor prognosis and lower disease-free and overall survival in GBC patients. These reports suggest that ncRNAs might be considered novel diagnostic and prognostic markers for the management of GBC. The present review recapitulates the association of various ncRNAs in the initiation and progression of GBC and the development of novel therapeutic strategies by exploring their functional and regulatory role.

Ovarian cancer is one of the deadliest gynecological cancers and the 7th most commonly occurring cancer in women globally. The 5 year survival rate is estimated to be less than 25 %, as in most cases, diagnosis occurs at an advanced stage. Despite recent advancements in treatment, clinical outcomes still remain poor, thus implicating the need for urgent identification of novel therapeutics for the treatment of this cancer. Ovarian cancer is considered a low immune reactive cancer as the tumor cells express insufficient neoantigens to be recognized by the immune cells and thus tend to escape from immune surveillance. Thus, in the recent decade, immunotherapy has gained significant attention and has rejuvenated the understanding of immune regulation in tumor biology. One of the critical immune checkpoints is programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis. Engagement of PD-1 to PD-L1 promotes immunologic tolerance and suppresses the effector T cells and maintains tumor Tregs, thus playing a crucial role in enhancing tumor survival. Recent studies are targeted to develop inhibitors that block this signal to augment the anti-tumor activity of immune cells. Also, compared to monotherapy, the combinatorial treatment of immune checkpoint inhibitors with small molecule inhibitors have shown promising results with improved efficacy and acceptable adverse events. The present review provides an overview of the PD-1/PD-L1 axis and role of non-coding RNAs in regulating this axis. Moreover, we have highlighted the various preclinical and clinical investigations on PD-1/PD-L1 immune checkpoint inhibitors and have discussed the limitations of immunotherapies in ovarian cancer.

Background Chronic diseases or non-communicable diseases are a major burden worldwide due to the lack of highly efficacious treatment modalities and the serious side effects associated with the available therapies. Purpose/study design A novel self-emulsifying formulation of curcumin with fenugreek galactomannan hydrogel scaffold as a water-dispersible non-covalent curcumin-galactomannan molecular complex (curcumagalactomannosides, CGM) has shown better bioavailability than curcumin and can be used for the prevention and treatment of chronic diseases. However, the exact potential of this formulation has not been studied, which would pave the way for its use for the prevention and treatment of multiple chronic diseases. Methods The whole transcriptome analysis (RNAseq) was used to identify differentially expressed genes (DEGs) in the liver tissues of mice treated with LPS to investigate the potential of CGM on the prevention and treatment of chronic diseases. Expression analysis using DESeq2 package, GO, and pathway analysis of the differentially expressed transcripts was performed using UniProtKB and KEGG-KAAS server. Results The results showed that 559 genes differentially expressed between the liver tissue of control mice and CGM treated mice (100 mg/kg b.wt. for 14 days), with adjusted p-value below 0.05, of which 318 genes were significantly upregulated and 241 were downregulated. Further analysis showed that 33 genes which were upregulated (log2FC > 8) in the disease conditions were significantly downregulated, and 32 genes which were downregulated (log2FC Conclusion Overall, our study showed CGM has high potential in the prevention and treatment of multiple chronic diseases.

Chronic inflammatory diseases are a major health concern nowadays as they cause a large number of deaths and most of the drugs developed for these diseases are not devoid of long-term adverse side effects. In addition, it is now well-established that chronic inflammation triggers the onset and development of many chronic diseases, such as cancer, cardiovascular diseases, diabetes and neurodegenerative diseases, etc. Therefore, there is an urgent need to control inflammation using novel anti-inflammatory agents that are safe, efficacious and affordable. Multiple lines of evidence suggest that many agents derived from Mother Nature have anti-inflammatory properties. One such agent, curcumin, originating from the golden spice, turmeric, has high potential in ameliorating chronic inflammatory diseases with lesser side effects. This compound has shown potential therapeutic effect against allergic rhinitis, asthma, chronic gastritis, chronic kidney disease, chronic prostatitis, gingivitis, inflammatory bowel disease, nephritis, oral lichen planus, oral mucositis, oral submucous fibrosis, osteoarthritis, peptic ulcer, periodontitis, rheumatoid arthritis, tropical pancreatitis, ulcerative proctitis, uveitis, etc. as evident from many preclinical and clinical studies. The current chapter discusses the anti-inflammatory potential of curcumin against these inflammatory diseases with special focus on clinical trials.

Tumor necrosis factor (TNF)-α, the most potent proinflammatory cytokine discovered to date, was first isolated in 1984 from human macrophage cells. Initially, it was thought to be a protein that was cytotoxic to tumor cells. But later, it was regarded as an agent that promotes inflammation and other chronic diseases found in humans. Currently, we know that the TNF superfamily (TNFS) has 19 members that perform a wide variety of functions via > 40 TNF receptors. Of TNFS members, TNF-α has been studied extensively and was found to be implicated in numerous autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, systemic lupus erythematosus, juvenile idiopathic arthritis, and diabetes. Thus, agents that can inhibit TNF-α have great potential for prevention and treatment of chronic diseases. To date, the U.S. Food and Drug Administration has approved many TNF-α blockers, such as etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab. These agents can block TNF-α actions and be used to treat different diseases. However, the uses of TNF-α blockers are not without serious adverse effects. Therefore, natural TNF-α blockers are best for developing safe, efficacious, and affordable agents for prevention and treatment of chronic diseases. The current review details the TNFS, functions of TNF-α in normal and disease conditions, roles of TNF-α blockers, and advantages and disadvantages.

Classical swine fever (CSF) is a highly contagious viral infection that affects domestic and wild pig population. The classical swine fever virus (CSFV) targets immune cells which perturb the immune functions causing immunopathological disorders such as immunosuppression, leukopenia and haemorrhage. In the present study, ELISA and quantitative real-time reverse transcription PCR (qRT-PCR) analysis was employed to determine cytokine profiles in pigs naturally infected with CSFV using whole blood assay (WBA) under field conditions. Significantly higher TNF-α, IL-10, and IL-6 expression levels were found in unvaccinated pigs infected with CSFV (group B) compared to vaccinated pigs that recovered after CSF (group A), the difference being statistically significant (p = 0.001). However, the expression of IFN-γ was significantly higher in group A compared to group B (p = 0.001). The findings of this field-supported study will help us to understand the immune biology of CSFV infection in infected pigs. The WBA technique can be used as a reliable, fast and feasible in vitro method to assess porcine cellular immune responses as it imitates the porcine blood conditions. Such studies could be of some value in determining the immune status of the ailing animals infected with CSFV. Keywords: classical swine fever virus; immune response; field conditions; interleukin; IFN-γ; TNF-α.

Elephant endotheliotropic herpesviruses (EEHVs) are the cause of acute hemorrhagic disease in endangered Asian and African elephants. In the present study, we report the incidence of EEHV infection and associated mortality in the captive elephant of Assam, India. Our result showed the gross morphology and histopathological changes of EEHV infection in the elephant. Moreover, the phylogenetic analysis of the polymerase, helicase, and GPCR genes from the infected tissue samples suggested the presence of EEHV1A virus.

Despite significant advancements made in the treatment of cancer during the past several decades, it remains one of the leading causes of death worldwide killing approximately 9.6 million people annually. The major challenge for therapeutic success is the development of chemoresistance in cancer cells against conventional chemotherapeutic agents via modulation of numerous survival and oncogenic signaling pathways. Therefore, sensitization of cancer cells to conventional drugs using multitargeted agents that suppress the survival and oncogenic pathways, in single or in combination, is an emerging strategy to overcome drug-resistance. During the last couple of decades, phytochemicals such as curcumin, resveratrol, tocotrienol and quercetin have emerged as potential chemosensitizing agents in cancer cells due to their less toxic and multitargeted properties. Numerous preclinical and clinical studies enumerated their potential to prevent drug resistance and sensitize cancer cells to chemotherapeutic agents by modulating several genes/proteins or pathways that regulate the key factors during the growth and progression of tumors such as inhibition of anti-apoptotic proteins, activation of pro-apoptotic proteins, reduced expression of different transcription factors, chemokines, enzymes, cell adhesion molecules, protein tyrosine kinases and cell cycle regulators. Therefore, natural chemosensitizing agents will have a special place in cancer treatment in the near future. This comprehensive review summarizes data obtained from various in vitro, in vivo and clinical studies to provide a new perspective for the application of agents obtained from "Mother Nature" as potential chemosensitizers for further cancer drug research and development.

Background According to GLOBOCAN 2018, oral cancer was reported as the second highest cancer prevalent in India. Despite the several therapies available for oral cancer treatment, tumor recurrence and distant metastasis persist. This study investigates the anticancer potential of Persicaria odorata, commonly known as Vietnamese coriander, used widely in traditional systems of medicine for the treatment of inflammation, stomach ailments, tumors, etc. Methods The crude methanolic extract of P. odorata (MPo) was prepared. The anticancer properties of MPo on SAS cells and other human oral squamous cell carcinoma cell line were evaluated using in vitro experimental conditions. The phytochemical constituents present in the MPo were also determined. Results Persicaria odorata possesses antiproliferative, antisurvival, antimetastatic activities, and induced cell cycle arrest in the G2 phase. It inhibited Akt-mammalian target of rapamycin (mTOR) signaling pathway and also downregulated the expression of essential proteins that are involved in tumorigenesis such as cyclin D1, cyclooxygenase 2 (COX2), survivin, matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor-A (VEGF-A). Moreover, the presence of flavonoids and quinones also revealed the anticancer activity of the plant. Conclusion Overall, our study concludes that P. odorata exhibits its anticancer properties through the downregulation of Akt/mTOR signaling pathway in a dose-dependent manner.

Oral cancer (OC) is a devastating disease that takes the lives of lots of people globally every year. The current spectrum of treatment modalities does not meet the needs of the patients. The disease heterogeneity demands personalized medicine or targeted therapies. Therefore, there is an urgent need to identify potential targets for the treatment of OC. Abundant evidence has suggested that the components of the protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) pathway are intrinsic factors for carcinogenesis. The AKT protein is central to the proliferation and survival of normal and cancer cells, and its downstream protein, mTOR, also plays an indispensable role in the cellular processes. The wide involvement of the AKT/mTOR pathway has been noted in oral squamous cell carcinoma (OSCC). This axis significantly regulates the various hallmarks of cancer, like proliferation, survival, angiogenesis, invasion, metastasis, autophagy, and epithelial-to-mesenchymal transition (EMT). Activated AKT/mTOR signaling is also associated with circadian signaling, chemoresistance and radio-resistance in OC cells. Several miRNAs, circRNAs and lncRNAs also modulate this pathway. The association of this axis with the process of tumorigenesis has culminated in the identification of its specific inhibitors for the prevention and treatment of OC. In this review, we discussed the significance of AKT/mTOR signaling in OC and its potential as a therapeutic target for the management of OC. This article also provided an update on several AKT/mTOR inhibitors that emerged as promising candidates for therapeutic interventions against OC/head and neck cancer (HNC) in clinical studies.

Classical swine fever is a highly contagious and economically important viral disease of pigs. Outbreaks of classical swine fever virus (CSFV) were recorded in different places in the Kamrup district of Assam in India between the years 2012 and 2014. The nucleotide sequences of the 10 CSFV isolates were analyzed based on the partial nucleotide sequences of the E2, 5'NTR and NS5B genes. Phylogenetic analysis indicated the dominance of subgroup 2.2 along with 2.1 strains in the northeast part of India. Variation in the nucleotide sequences of E2, 5'NTR and 3'NS5B genes of CSFV allows tracking changes in the virus population over time. The study will provide epidemiological information useful for assessing CSFV circulating genogroups in India.

Classical swine fever virus (CSFV) is the causative agent of a highly contagious disease in swine. The disease is endemic in different parts of the world and vaccination is the only way to protect pigs from CSFV infection. The virus surface protein E2 is the major immunogenic protein eliciting protective immunity against CSFV infection in swine. The whole virus antigen cannot differentiate CSFV from other pestiviruses as it cross reacts with border disease and bovine viral diarrhoea viruses. Commercial available ELISA is based on the whole CSFV particle and can lead to false positive results. Moreover, the available commercial ELISA is not cost effective. In the present study, a recombinant E2 protein based single serum dilution ELISA was developed which showed enhanced sensitivity, specificity and accuracy as compared to commercial CSFV detection ELISA. The recombinant E2 protein based ELISA could be an alternate to existing diagnostics against CSFV infection in pigs.

Classical swine fever virus (CSFV) is the causative agent of a highly contagious disease, hog cholera in pigs. The disease is endemic in many parts of the world and vaccination is the only way to protect the animals from CSFV infection. Wild hogs belong to the species Sus Scrofa Cristatus under the family Suidae are quite susceptible to CSFV infection. The epidemiological role concerning classical swine fever (CSF) in India is largely unknown. We report here the three isolated cases of CSF in wild hogs from three National parks, namely Kaziranga National Park, Manas National Park and Jaldapara National Park, from north-east part of India. The post-mortem and histopathological findings were clearly indicative for CSFV infection. The presence of CSFV genome was demonstrated in several organs and tissues collected from hogs died due to viral infection. In addition, CSF-specific antibodies were detected in two wild hogs as well as in eighteen feral pigs from the same locations. The phylogenetic analysis of the partial E2 protein gene and 5' untranslated region of CSFV isolates from the wild hog showed identities with genotype 2.2 of the Indian isolates. Occurrence of CSF in wild hogs may pose a potent threat in the epidemiology of the virus in Northeast part of India. To the best of our knowledge, the report presented in the manuscript is the first comprehensive report on CSF in wild hogs form Northeast India. The findings reported would help us to understand the epidemiology and biology of CSFV in wild animals.

Two outbreaks of orf virus (ORFV) (a parapoxvirus) infection in goats, which occurred in Golaghat and Kamrup districts of Assam, a northeastern part of India, were investigated. The disease was diagnosed by standard virological and molecular techniques. The entire protein-coding region of B2L gene of two isolates were cloned and sequenced. Phylogenetic analysis based on B2L amino acid sequences showed that the ORFVs identified in these outbreaks were closely related to each other and both were closer to ORFV-Shahjahanpur 82/04 isolate from north India. The present study revealed that the precise characterization of the genomic region (B2L gene) might provide evidence for the genetic variation and movement of circulating ORFV strains in India.