Sterol regulator element binding proteins (SREBPs) are a family of transcription factors involved in the biogenesis of cholesterol, fatty acids and triglycerides. They also regulate physiological functions of many organs, such as thyroid, brain, heart, pancreas and hormone synthesis. Beside the physiological effects, SREBPs participate in some pathological processes, diabetes, endoplasmic reticulum stress, atherosclerosis and chronic kidney disease associated with SREBP expression changes. In the liver, SREBPs are involved in the pathogenesis of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, hepatitis and hepatic cancer. There are several SREBP inhibitors that have potential for treating obesity, diabetes and cancer. This review assesses the recent findings about the roles of SREBPs in the physiology of organs’ function and pathogenesis of liver diseases.

Syphilitic hepatitis in adults is not frequently found in the population and is easily misdiagnosed. The incidence of viral hepatitis is increasing year by year, concomitantly increasing the importance of obtaining a systematic understanding of the clinical features and treatment strategies for this disease. There is, however, a lack of published definitive data regarding the clinical characteristics, diagnosis and standard treatment options for this disease. Searches were made using the MEDLINE database of PubMed and OVID for syphilitic hepatitis publications from 1951 to 2017 in an attempt to analyze and summarize the clinical characteristics.

Despite significant improvements in outcomes after liver transplantation, many patients continue to die on the waiting list, while awaiting an available organ for transplantation. Organ shortage is not only due to an inadequate number of available organs, but also the inability to adequately assess and evaluate these organs prior to transplantation. Over the last few decades, ex-vivo perfusion of the liver has emerged as a useful technique for both improved organ preservation and assessment of organs prior to transplantation. Large animal studies have shown the superiority of ex-vivo perfusion over cold static storage. However, these studies have not, necessarily, been translatable to human livers. Small animal studies have been essential in understanding and improving this technology. Similarly, these results have yet to be translated into clinical use. A few Phase 1 clinical trials have shown promise and confirmed the viability of this technology. However, more robust studies are needed before ex-vivo liver perfusion can be widely accepted as the new clinical standard of organ preservation. Here, we aimed to review all relevant large and small animal research, as well as human liver studies on normothermic ex-vivo perfusion, and to identify areas of deficiency and opportunities for future research endeavors.

Background and Aims: Sustained virologic response is evaluated by single-step reverse transcription (SRT) PCR assay, which assesses hepatitis C virus (HCV) clearance from plasma but not from tissues such as peripheral blood mononuclear cells (PBMCs). Persistence of HCV RNA in PBMCs beyond end of treatment (EOT) is associated with nonresponse. Our goal was to measure intra-PBMC HCV RNA levels during oral antiviral therapy according to the HCV therapy follow-up fractionation (CTF2) protocol.

Methods: Compensated chronic HCV patients (n = 2 78 SRT-PCR positive) were scheduled to receive oral antiviral therapy. Subjects were followed-up by SRT and intra-PBMCs HCV RNA PCR at the end of the 2nd, 6th, 10th, 14th, 18th and 24th weeks to evaluate virus clearance from plasma and PBMCs, respectively. The CTF2 protocol evaluated SRT and PBMC PCR status at each follow-up point for determining therapy continuation or interruption to address cost effectiveness.

Results: All patients tested negative by SRT PCR after therapy for 2 weeks. Application of the CTF2 protocol revealed: a) increasing HCV clearance rate from 75.9% at the end of 10th week to 90.3% at the end of 24th week (p < 0.00001); b) faster clearance of HCV from plasma compared to PBMCs at each point of follow-up until the 18th week (p < 0.05); c) higher viral elimination rates diagnosed by PBMC HCV RNA PCR(−) compared to PBMC HCV RNA PCR(+) from the 6th to 24th week of treatment (p < 0.0001); d) higher over-time increase curve of combined plasma and PBMC HCV RNA determined negativity compared to the decline in positivity curves by PBMC PCR at the 6th-18th week compared to the 24th week (p < 0.01)—these results validated treatment continuation; and e) solitary evaluation of EOT sustained HCV infection and relapses by PBMC HCV RNA (p < 0.001).

Conclusions: Early elimination of serum and tissue (PBMC) HCV infection by oral antiviral therapy can be achieved and evaluated during a cost-effective CTF2 protocol application.

Long QT syndrome (LQTS) is a rare primary cardiac electrophysiological disorder with characteristic symptoms of syncope, tachyarrhythmia and torsades-de-pointes. It is the outcome of mutations in genes encoding ion channels that function as voltage regulators. Heat shock protein (HSP) 90 is a molecular chaperone that plays vital roles in a variety of cellular processes, one of which is folding of nascent polypeptide chains into their native forms. The main objective of this study was to screen for HSP90 Q488H (C > G) polymorphism in patients with LQTS and identify its risk towards LQTS manifestation.

Allele-specific PCR was employed to genotype 49 LQTS patients, 71 first-degree relatives (FDRs) and 219 controls for the HSP90 Q488H polymorphism. The genotypes were statistically evaluated to assess their association with the risk of LQTS. Further, bioinformatic analysis was performed to validate the statistical findings.

Genotyping and statistical evaluation revealed a significant association of the CG genotype with LQTS, pointing towards a heterozygote disadvantage in the patients. The GG and CG genotypes showed a significant association with LQTS in the FDRs. Secondary pre-mRNA structure of the variant allele ‘G’ was found to be more stable than the wild-type structure.

Individuals harboring the heterozygous “CG” genotype are at increased risk for LQTS. In the FDRs, especially, the females harboring the “CG” and “GG” genotypes could transmit the risk allele to the future generation, giving rise to a disadvantage towards LQTS. It is imperative that all FDRs undergo carrier detection and/or prenatal diagnosis to prevent the recurrence of dominant-negative effect leading to sudden cardiac death events among the current and future generations.

The present study deals with a computational model of the transport and retention of drug within the arterial wall eluted from a drug-eluting stent, to enhance our understanding of the performance of this device. We considered a two-species model (free and bound) incorporating a reversible reaction to describe drug interactions with the constituents of the arterial wall. An axisymmetric model of drug delivery from a pair of stent struts has been developed, where the transport of free drug is modelled as an unsteady reaction-diffusion process, while the bound drug, assuming complete immobilization in the tissue, is modeled as an unsteady reaction process. The model also took into account a second-order binding process that describes a saturating reversible binding and time-dependent release kinetics of the drug-eluting stent. Considering that diffusion takes place over a tortuous path in a porous media, the effects of porosity and tortuosity on diffusion cannot be ruled out from this present investigation.

An explicit finite-difference scheme is leveraged to tackle numerically the governing equations of motion, together with the physiologically realistic boundary conditions.

The quantitative effects of significant factors, such as Peclet number (PeT), Damköhler number (Da), tortuosity, porosity, interstrut distance and time-dependent release kinetics of drug-eluting stent, on the distribution and retention of drug are determined graphically.

Predicted results are consistent with several existing results in the literature, which certainly validates the applicability of the model considered.

The CYP2C19*2 allele is associated with reduced clopidogrel bioactivation, increasing the risk of complications after percutaneous coronary intervention (PCI), particularly stent thrombosis. Recently published data suggests that CYP2C19*2 allele carriers have a higher risk for in-stent restenosis (ISR) after endovascular treatment. Very few studies have investigated the relationship between CYP2C19*2 and coronary ISR, with no significant association reported. The objective of this study was to assess the relationship between CYP2C19*2 allele carrier status and coronary ISR.

Patients with previous PCI with stenting and who were scheduled for elective PCI after coronary angiogram were recruited from the cardiac catheterization suite over a 12-month period. The angiography report of each patient was perused to identify patients requiring PCI due to ISR. For patients with angiography-confirmed ISR, date of previous PCI to the restenosed stent was noted. CYP2C19*2 genotyping was undertaken using a TaqMan® Drug Metabolism assay. The association between CYP2C19*2 allele carrier status and incidence of coronary ISR within 1 year was assessed using Fisher’s exact test (p < 0.05 significance) and by calculating the odds ratio (OR) with a 95% confidence interval (CI).

Of the 82 patients with previous PCI, 29 (35.4%) had angiography-confirmed ISR (12 carriers, 17 non-carriers of CYP2C19*2). In 13 (44.8%) of these patients, the restenosed stent was deployed within 1 year and the patients were on clopidogrel therapy at the time of repeat PCI (8 carriers, 5 non-carriers of CYP2C19*2). The association between CYP2C19*2 allele carrier status and ISR within 1 year was not statistically significant (Fisher’s exact p = 0.067; OR: 4.80, 95% CI: 0.98–23.54, p = 0.053).

Despite a higher proportion of CYP2C19*2 allele carriers exhibiting ISR within 1 year compared to non-carriers, the association was not statistically significant. This result may be attributed to the small sample size, and larger prospective studies are recommended to further assess this association.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related deaths worldwide. Curative resection is frequently limited in Hong Kong by hepatitis B virus-related cirrhosis, and liver transplantation is the treatment of choice. Liver transplantation has been shown to produce superior oncological benefits, when compared to hepatectomy for HCC. New developments in the context of patient selection criteria, modification of organ allocation, bridging therapy, salvage liver transplantation and pharmaceutical breakthrough have improved the survival of HCC patients. In this article, we will share our experience in transplanting hepatitis B virus-related HCC patients in Hong Kong and discuss the recent progress in several areas of liver transplantation.

Since the beginning of the century, viral infection has become a widespread problem to public health globally. Recently, the latest newcomer of the Flaviviridae family, the Zika virus, has emerged as a potential global threat to human health. Due to lack of sufficient data at present, Zika infection has become a major cause of Zika fever, central nervous system malformations such as microcephaly, severe neuroimmunopathology, fetal abnormalities, and recently Guillain-Barre syndrome. The lack of genomic as well as proteomic information keeps the Zika virus under examination by a multitude of researchers. The rapid increase in Zika viral infections has been classified as a public health emergency by the World Health Organization. Neither preventive antiviral drugs nor effective vaccines are available on the market for combating Zika infection. Urgent innovative research is necessary to facilitate the development of protective and fruitful therapeutic agents, to improve lifespan of individuals throughout the world. Thus, we present this review to summarize the current research findings for Zika viral infection and to highlight the importance of computational drug discovery in the development of potent antiviral inhibitors against the Zika virus. We also anticipate that the information in this review will present a valuable opportunity for the prediction of efficient novel therapeutic remedies for controlling Zika.

Spontaneous or intended conversion of atrial fibrillation (AF) to sinus rhythm is associated with a short-term increase from baseline risk of clinical thromboembolism. Guidelines suggest performing cardioversion without prior execution of trans esophageal echo (TEE) if the patient has completed a month of anticoagulation with warfarin (in the therapeutic international normalized ratio range) or non-vitamin K antagonist oral anticoagulants (NOACs).

We performed TEE echo in 100 consecutive patients taking NOACs or warfarin for 1 month or more, to see if there was evidence of left arterial appendage thrombi or extremely low flow velocity (<40 cm/s) that can increase risk of ischemic events after cardioversion.

Even in patients with correct anticoagulation therapy, thrombi can be found in the left atrial appendage. For this reason, until further data are present, we suggest executing TEE before direct current cardioversion. Moreover, NOAC was shown to be safe for use before cardioversion. The only exception was with rivaroxaban, so we suggest further analysis with larger samples to determine the mechanisms underlying this finding.

Even if cardioversion can be performed without prior TEE after 1 month of anticoagulation therapy, we think that (except in patients with very low risk of thrombosis) it is preferable to execute this exam before trying to restore sinus rhythm.

Non-alcoholic fatty liver disease (NAFLD), the most common cause of liver disease, affects approximately 75 to 100 million Americans. Patients with concurrent NAFLD and type 2 diabetes mellitus have a higher risk of progressing to advanced fibrosis and non-alcoholic steatohepatitis compared to non-diabetics. Lifestyle modifications, including weight loss, remain the mainstay of treatment for NAFLD, as there are no medications currently indicated for this disease state. Anti-diabetic pharmacologic therapies aimed at improving insulin sensitivity and decreasing insulin production have been studied to determine their potential role in slowing the progression of NAFLD. In this review, we focus on the evidence surrounding anti-diabetic medications and their ability to improve disease progression in patients with NAFLD.

Tight junction and cell polarity proteins are paramount to epithelial cell polarity and transport. In vivo studies have shown the differential expression of tight junctions in colorectal cancer, with little to no human data to corroborate those findings. We investigated whether tight junction genes were differentially expressed in human colon cancer versus normal controls.

Total RNA was extracted from fresh frozen tumor tissues and normal adjacent tissues of 6 patients who were diagnosed with primary colon cancer as well as from normal mucosa of 5 unrelated polyp-free individuals. We used the Qiagen RT2 Profiler PCR array to determine the expression of 84 genes in the tight junction pathway. Student’s t-test was used to compare gene expression levels between cancer tissues and normal mucosa using normalized gene expression data.

Compared with normal mucosa, significant up-regulation of the claudin 1 (CLDN1) gene (fold-change = 16, p = 0.001) but down-regulation of the AMOTL1, CLDN5, JAM2 and TIAM1 genes (fold-change > 2, p < 0.05) were seen in colon cancer tissue.

We observed the differential expression of CLDN, AMOTL1, JAM2 and TIAM1 in colon cancer versus normal mucosa. Further larger studies are warranted to investigate the role of tight junction and cell polarity proteins in the progression of human colon tumors.

Background and Aims: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.

Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA <200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281.

Results: At the end of 48 and 96 weeks’ treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks’ treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg <1500 IU/mL and week 24 HBsAg <200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss.

Conclusions: Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

The role of metabolism (basal metabolic rate (BMR)) in asthma remains dubious. Seasonal variations are reported in both BMR and asthma, with the former increasing in winter and decreasing in summer. Correlation between metabolism and asthma treatment is not obvious in the literature; therefore, it was planned to assess role of substances which alter metabolism in managing asthma.

This was a randomized double-blind active control trial, in which 400 confirmed asthma cases were divided into two groups (group 1 (control) and group 2 (study)), with group 2 further subdivided into two (subgroups 2A and 2B). The study period was from January to December 2016. During attack, group 2A was given kitchen spices (cloves, bay leaf, black pepper; substance A) and 2B was given cool substances (rose petal jam; substance B). The control group was given inhaled levosalbutamol. Symptoms and peak expiratory flow rate (PEFR) were recorded. Improvement was suggested by reduction in symptoms and improvement in PEFR. Review of symptoms was done at 24 and 72 h and of PEFR at 72 h after the therapy. Statistical significance of differences between group 1 and 2A and 2B was calculated by the chi-square test by using SPSS 20 software.

Exacerbations were found in February (season: winter), March (spring), August (rainy) and October (autumn). In February and March, the response was significant with substance A (p < 0.001), but substance B had poor response. In August and October, the response was significant with substance B (p < 0.001), and substance A had insignificant response.

Substances which increase BMR are helpful in winters and high metabolic state of the body, and conversely. Change in metabolism possibly effects heat and water losing/preserving effect of the body, including related to the respiratory tract (thermoregulation), and lessens inflammation in the respiratory tract.