Viral hepatitis: A global burden needs future directions for the management

Viral hepatitis is an acute or chronic liver disease due to the infection from Hepatitis A,B,C,D and E viruses.It can cause severe liver damage such as cirrhosis,liver failure and liver cancer.To avoid such fatal complications,hepatitis patients must be diagnosed,pathologized and treated as soon as possible.Furthermore,these hepatitis viruses infect through different routes,resulting in distinct disease pathologies,severity and even the need for specific treatment strategies to combat the infection.

Endoscopic ultrasound-guided injectable therapy for pancreatic cancer:A systematic review

BACKGROUND Given the low survival rate in pancreatic cancer,new therapeutic techniques have been explored,especially for unresectable or borderline resectable disease.Endoscopic ultrasound(EUS)provides real-time imaging and minimally invasive access for local and targeted injection of anti-tumor agents directly into the pancreatic tumor.Limited studies have been reported using this technique for the treatment of pancreatic ductal adenocarcinoma(PDAC).AIM To evaluate the progress made with EUS-guided injectable therapies in the treatment of PDAC.METHODS All original articles published in English until July 15,2021,were retrieved via a library-assisted literature search from Ovid Evidence-Based Medicine Reviews and Scopus databases.Reference lists were reviewed to identify additional relevant articles.Prospective clinical studies evaluating the use of EUS-guided injectable therapies in PDAC were included.Studies primarily directed at non-EUS injectable therapies and other malignancies were excluded.Retrieved manuscripts were reviewed descriptively with on critical appraisal of published studies based on their methods and outcome measures such as safety,feasibility,and effectiveness in terms of tumor response and survival.Heterogeneity in data outcomes and therapeutic techniques limited the ability to perform comparative statistical analysis.RESULTS A total of thirteen articles(503 patients)were found eligible for inclusion.The EUS-injectable therapies used were heterogeneous among the studies consisting of immunotherapy(n=5)in 59 patients,chemotherapy(n=1)in 36 patients,and viral and other biological therapies(n=7)in 408 patients.Eleven of the studies reviewed were single armed while two were double armed with one randomized trial and one non-randomized comparative study.Overall,the included studies demonstrated EUS-guided injectable therapies to be safe and feasible with different agents as monotherapy or in conjunction with other modalities.Promising results were also observed regarding their efficacy and survival parameters in patients with PDAC.CONCLUSION EUS-guided injectable therapies,including immunotherapy,chemotherapy,and viral or other biological therapies have shown minimal adverse events and potential efficacy in the treatment of PDAC.Comparative studies,including controlled trials,are required to confirm these results in order to offer novel EUS-based treatment options for patients with PDAC.

Current and emerging therapeutic approaches for colorectal cancer:A comprehensive review

Colorectal cancer(CRC)affects 1 in 23 males and 1 in 25 females,making it the third most common cancer.With roughly 608000 deaths worldwide,CRC accounts for 8%of all cancer-related deaths,making it the second most common cause of death due to cancer.Standard and conventional CRC treatments include surgical expurgation for resectable CRC and radiotherapy,chemotherapy,immunotherapy,and their combinational regimen for non-resectable CRC.Despite these tactics,nearly half of patients develop incurable recurring CRC.Cancer cells resist the effects of chemotherapeutic drugs in a variety of ways,including drug inactivation,drug influx and efflux modifications,and ATPbinding cassette transporter overexpression.These constraints necessitate the development of new target-specific therapeutic strategies.Emerging therapeutic approaches,such as targeted immune boosting therapies,non-coding RNA-based therapies,probiotics,natural products,oncolytic viral therapies,and biomarkerdriven therapies,have shown promising results in preclinical and clinical studies.We tethered the entire evolutionary trends in the development of CRC treatments in this review and discussed the potential of new therapies and how they might be used in conjunction with conventional treatments as well as their advantages and drawbacks as future medicines.

Restoring axonal localization and transport of transmembrane receptors to promote repair within the injured CNS: a critical step in CNS regeneration

Each neuronal subtype is distinct in how it develops,responds to environmental cues,and whether it is capable of mounting a regenerative response following injury.Although the adult central nervous system（CNS） does not regenerate,several experimental interventions have been trialled with successful albeit limited instances of axonal repair.We highlight here some of these approaches including extracellular matrix（ECM） modification,cellular grafting,gene therapy-induced replacement of proteins,as well as application of biomaterials.We also review the recent report demonstrating the failure of axonal localization and transport of growth-promoting receptors within certain classes of mature neurons.More specifically,we discuss an inability of integrin receptors to localize within the axonal compartment of mature motor neurons such as in the corticospinal and rubrospinal tracts,whereas in immature neurons of those pathways and in mature sensory tracts such as in the optic nerve and dorsal column pathways these receptors readily localize within axons.Furthermore we assert that this failure of axonal localization contributes to the intrinsic inability of axonal regeneration.We conclude by highlighting the necessity for both combined therapies as well as a targeted approach specific to both age and neuronal subtype will be required to induce substantial CNS repair.

Potent antitumoral effects of a novel gene-viral therapeutic system CNHK300-mEndostatin in hepatocellular carcinoma

The expression of therapeutic gene and its anti-tumor effects will beaugmented and a synergism of oncolytic virus with the therapeutic gene is speculated. This study wasundertaken to assess the anti-tumor effects of a novel gene-viral therapeutic systemCNHK300-mEndostatin ( CNHK300-mE) in hepatocellular carcinoma (HCC). A novel gene-viral therapeuticsystem named CNHK300-mE was constructed using the human telomerase reverse transcriptase (hTERT)promoter to drive the expression of the adenovirus El A gene and cloning the therapeutic gene mouseendostatin into the adenovirus genome. By the tissue culture infectious dose 50 (TCID50) method andcytoviability assay, the replicative and cytolytic capabilities of CNHK300-mE in two HCC lines (HepGII and Hep3B) and one normal cell line ( MRC-5 ) were analyzed, and the transgene expressions ofmouse endostatin in vitro and in vivo were detected by Western blotting and ELISA assay. Tumorgrowth suppression and anti-angiogenesis effects in vivo were investigated using nude micexenografts model derived from SMMC-7721 HCC cells. The 3296-fold replicating capacity of CNHK300-mEin HCC cell lines versus in the normal cell line at 96 hours post infection and the 25 -foldeffective dose for killing 50% cells ( ED50) in the normal cell line versus HCC cell lines, whichwere both superior to ONYX-015, were observed. Tumor growth suppression of CNHK300-mE superior toeither Ad-mE or ONYX-015 was demonstrated (P < 0. 01) and the anti-angiogenic effects in vivosuperior to Ad-mE were also observed with immunohistochemical staining of von Willebrand factor. Incomparison with non-replicative adenovirus Ad-mE, the transgene expression of mE mediated byCNHK300- in vivo (P<0.05). Being capable of replicating in and lysing the telomerase-positive HCCcells and mediating effective expression of the therapeutic gene in vitro and in vivo, the novelgene-viral therapeutic system CNHK300-mE is potentially effective in the treatment of HCC.

Tailoring minimalist self-assembling peptides for localized viral vector aene deliverv

Viral vector gene delivery is a promising technique for the therapeutic administra- tion of proteins to damaged tissue for the improvement of regeneration outcomes in various disease settings including brain and spinal cord injury, as well as autoimmune diseases. Though promising results have been demonstrated, limitations of viral vectors, including spread of the virus to distant sites, neutralization by the host immune system, and low transduction efficiencies have stimulated the investigation of biomaterials as gene delivery vehicles for improved protein expression at an injury site. Here, we show how N- fluorenylmethyloxycarbonyl （Fmoc） self-assembling peptide （SAP） hydrogels, designed for tissue-specific central nervous system （CNS） applications via incorporation of the laminin peptide sequence isoleucine-lysine-valine-alanine- valine （IKVAV）, are effective as biocompatible, localized viral vector gene delivery vehicles in vivo. Through the addition of a C-terminal lysine （K） residue, we show that increased electrostatic interactions, provided by the additional amine side chain, allow effective immobilization of lentiviral vector particles, thereby limiting their activity exclusively to the site of injection and enabling focal gene delivery in vivo in a tissue-specific manner. When the C-terminal lysine was absent, no difference was observed between the number of transfected cells, the volume of tissue transfected, or the transfection efficiency with and without the Fmoc-SAP. Importantly, immobilization of the virus only affected transfection cell number and volume, with no impact observed on transfection efficiency. This hydrogel allows the sustained and targeted delivery of growth factors post injury. We have established Fmoc-SAPs as a versatile platform for enhanced biomaterial design for a range of tissue engineering applications.