Deciphering the role of transforming growth factor-beta 1 as a diagnostic-prognostic-therapeutic candidate against hepatocellular carcinoma

Transforming growth factor-beta(TGF-β)is a multifunctional cytokine that performs a dual role as a tumor suppressor and tumor promoter during cancer progression.Among different ligands of the TGF-βfamily,TGF-β1 modulates most of its biological outcomes.Despite the abundant expression of TGF-β1 in the liver,steatosis to hepatocellular carcinoma(HCC)progression triggers elevated TGF-β1 levels,contributing to poor prognosis and survival.Additionally,elevated TGF-β1 levels in the tumor microenvironment create an immunosuppressive stage via various mechanisms.TGF-β1 has a prime role as a diagnostic and prognostic biomarker in HCC.Moreover,TGF-β1 is widely studied as a therapeutic target either as monotherapy or combined with immune checkpoint inhibitors.This review provides clinical relevance and up-to-date information regarding the potential of TGF-β1 in diagnosis,prognosis,and therapy against HCC.

Critical biomarkers of hepatocellular carcinoma in body fluids and gut microbiota

Hepatocellular carcinoma(HCC)is the most prevalent primary liver cancer and one of the major causes of cancer-related death.The development of specific noninvasive or diagnostic markers from blood,urine and feces may represent a valuable tool for detecting HCC at an early stage.Biomarkers are considered novel potential targets for therapeutic intervention.It helps in the prediction of prognosis or recurrence of HCC,and also assist in the selection of appropriate treatment modality.We summarize the most relevant existing data about various biomarkers that play a key role in the progression of HCC.

Analgesic and Anti-Arthritic Effect of <i>Enicostemma littorale</i>Blume

Enicostemma littorale (Blume), the folk medicine is used for rheumatic pain and it was selected for scientific validation. The 85% methanolic extract obtained from the whole plant of Enicostemma littorale has been assessed for analgesic and anti-inflammatory activity. The analgesic activity has been evaluated by hot plate and tail immersion method and the anti-inflammatory and antioxidant activities are evaluated by Complete Freund’s adjuvant induced arthritic model. The results of the evaluation of analgesic activity in hot plate and tail immersion method revealed that the extract exhibits significant activity at 150 mg/kg body weight and the effect is found to increase dose dependently. In Freund’s adjuvant induced arthritis, Enicostemma littorale is found to decrease the paw volume (15.81%). Significant protection is also observed by elevating antioxidant enzymes. In conclusion, the 85% methanolic extract of Enicostemma littorale possesses significant analgesic and anti-inflammatory activities in Freund’s adjuvant induced arthritic model in rats.

Smart polymers for the controlled delivery of drugs–a concise overview

Smart polymers have enormous potential in various applications.In particular,smart polymeric drug delivery systems have been explored as“intelligent”delivery systems able to release,at the appropriate time and site of action,entrapped drugs in response to specific physiological triggers.These polymers exhibit a non-linear response to a small stimulus leading to a macroscopic alteration in their structure/properties.The responses vary widely from swelling/contraction to disintegration.Synthesis of new polymers and crosslinkers with greater biocompatibility and better biodegradability would increase and enhance current applications.The most fascinating features of the smart polymers arise from their versatility and tunable sensitivity.The most significant weakness of all these external stimuli-sensitive polymers is slow response time.The versatility of polymer sources and their combinatorial synthesis make it possible to tune polymer sensitivity to a given stimulus within a narrow range.Development of smart polymer systems may lead to more accurate and programmable drug delivery.In this review,we discuss various mechanisms by which polymer systems are assembled in situ to form implanted devices for sustained release of therapeutic macromolecules,and we highlight various applications in the field of advanced drug delivery.

Elucidation of regulatory interaction networks underlying human prostate adenocarcinoma

The incidence of prostate cancer is rising in the Asia-Pacific region as well as other countries. Androgen-ablation therapy is clinically useful in the androgen-dependent phenotype however, many patients progress to hormone refractory prostate cancer that is difficult to treat and needs newer interventions that are more effective. The objective of this study was to determine functionally-relevant biological networks, to appreciate the potential crosstalk between signaling members, and to identify biomarker signatures in prostate cancer. We used microarray analyses to identify key genes that were upregulated or down regulated at least five-fold in human prostate cancer and constructed canonical interaction networks that are important in prostate cancer through metabolomics analyses. Our prostate cancer network architecture revealed several key biomarkers including ERK1/2, JNK, p38, MEK, PI3 K, NFκB, AP-1, 14-3-3, VEGF, PDGF, Rb, WNT8 A, WNT10 A, CD44, ESR2, FSH and LH. Furthermore, the top ten transcription factors identified by TFBS-association signature analysis in the regulatory elements of co-regulated biomarkers were delineated, which may crosstalk with upstream or downstream genes elicited in our network architecture. Taken together, our results demonstrate that the regulatory interaction networks in prostate cancer provide a universal view of crosstalk between important biomarkers, i.e., key players in the pathogenesis of this disease. This will facilitate more rapid screening of functional biomarkers in early/intermediate drug discovery.

Differential signaling regulatory networks governing hormone refractory prostate cancers

To understand the organization of the biological networks that might potentially govern the pathogenesis of hormone refractory prostate cancer(HRPC), we investigated the transcriptional circuitry and signaling in androgen-dependent 22Rv1 and MDA PCa 2b cells, androgen- and estrogen-dependent LNCaP cells, and androgen-independent DU 145 and PC-3 prostate cancer(PCa) cell lines. We used microarray analyses, quantitative real-time PCR, pathway prediction analyses, and determination of Transcription Factor Binding Site(TFBS) signatures to dissect HRPC regulatory networks. We generated graphical representations of global topology and local network motifs that might be important in prostate carcinogenesis. Many important putative biomarker ‘target hubs' were identified in the current study including AP-1, NF-?B, EGFR, ERK1/2, JNK, p38 MAPK, TGF beta, VEGF, PDGF, CD44, Akt, PI3 K, NOTCH1, CASP1, MMP2 and AR. Our results suggest that complex cellular events including autoregulation, feedback loops and cross-talk might govern progression from early lesion to clinically diagnosed PCa, as well as metastatic potential of pre-existent high-grade prostate intraepithelial neoplasia(HG-PIN) and/or advancement to HRPC. The identification of TFBS signatures for TCF/LEF, SOX9 and ELK1 in the regulatory elements suggests additional biomarkers for the potential development of chemopreventive/therapeutic strategies against PCa. Taken together, in this study, we have identified putative biomarker ‘target hubs' in the architecture of PCa signaling networks, and investigated TFBS signatures that might enhance our understanding of key regulatory nodes in the progression and pathogenesis of HRPC.