Non-alcoholic fatty liver disease and its related complications are becoming one of the most important health problems globally. The liver functions as both a metabolic and an immune organ. The ...crosstalk between hepatocytes and intrahepatic immune cells plays a key role in coordinating a dual function of the liver in terms of the protection of the host from antigenic overload as a result of receiving nutrients and gut microbiota antigenic stimulation via facilitating immunologic tolerance. B cells are the most abundant lymphocytes in the liver. The crucial role of intrahepatic B cells in energy metabolism under different immune conditions is now emerging in the literature. The accumulating evidence has demonstrated that the antibodies and cytokines produced by B cells in the microenvironment play key and distinct roles in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Herein, we have aimed to consolidate and update the current knowledge about the pathophysiological roles of B cells as well as the underlying mechanisms in energy metabolism. Understanding how B cells can exacerbate and suppress liver damage by exploiting the antibodies and cytokines they produce will be of great importance for designing B-cell targeting therapies to treat various liver diseases.
Social distancing under the COVID-19 pandemic has restricted access to community services for older adults with neurocognitive disorder (NCD) and their caregivers. Telehealth is a viable alternative ...to face-to-face service delivery. Telephone calls alone, however, may be insufficient. Here, we evaluated whether supplementary telehealth via video-conferencing platforms could bring additional benefits to care-recipient with NCD and their spousal caregivers at home.
Sixty older adults NCD-and-caregiver dyads were recruited through an activity center.
The impact of additional services delivered to both care-recipient and caregiver through video conference (n = 30) was compared with telehealth targeted at caregivers by telephone only (n = 30), over 4 weeks in a pretest-post-test design. Interviews and questionnaires were conducted at baseline and study's end.
Supplementary telemedicine had averted the deterioration in the Montreal Cognitive Assessment evident in the telephone-only group (η
= 0.50). It also reversed the falling trend in quality of life observed in the telephone only group (QoL-AD, η
= 0.23). Varying degrees of improvements in physical and mental health (Short-Form 36 v2), perceived burden (Zarit Burden Interview Scale) and self-efficacy (Revised Caregiving Self-Efficacy Scale) were observed among caregivers in the video-conferencing group, which were absent in the telephone-only group (η
= 0.23-0.51).
Telemedicine by video conference was associated with improved resilience and wellbeing to both people with NCD and their caregivers at home. The benefits were visible already after 4 weeks and unmatched by telephone alone. Video conference as the modus operandi of telehmedicine beyond the context of pandemic-related social distancing should be considered.
Recent research has shown that the adhesion G protein-coupled receptor F1 (
also known as
) is an oncogene. The evidence is mainly based on high expression of
in numerous cancer types, and knockdown
...can reduce the cell migration, invasion, and proliferation.
is, however, mostly expressed in the liver of healthy individuals. The function of
in liver has not been revealed. Interestingly, expression level of hepatic
is dramatically decreased in obese subjects. Here, the research examined whether
has a role in liver metabolism.
We used recombinant adeno-associated virus-mediated gene delivery system, and antisense oligonucleotide was used to manipulate the hepatic
expression level in diet-induced obese mice to investigate the role of
in hepatic steatosis. The clinical relevance was examined using transcriptome profiling and archived biopsy specimens of liver tissues from non-alcoholic fatty liver disease (NAFLD) patients with different degree of fatty liver.
The expression of
in the liver was directly correlated to fat content in the livers of both obese mice and NAFLD patients. Stearoyl-coA desaturase 1 (
), a crucial enzyme in hepatic de novo lipogenesis, was identified as a downstream target of
by RNA-sequencing analysis. Treatment with the liver-specific
inhibitor MK8245 and specific shRNAs against
in primary hepatocytes improved the hepatic steatosis of
-overexpressing mice and lipid profile of hepatocytes, respectively.
These results indicate
regulates hepatic lipid metabolism through controlling the expression of
. Downregulation of
expression can potentially serve as a protective mechanism to stop the overaccumulation of fat in the liver in obese subjects. Overall, the above findings not only reveal a new mechanism regulating the progression of NAFLD, but also proposed a novel therapeutic approach to combat NAFLD by targeting
.
This work was supported by the National Natural Science Foundation of China (81870586), Area of Excellence (AoE/M-707/18), and General Research Fund (15101520) to CMW, and the National Natural Science Foundation of China (82270941, 81974117) to SJ.
Background. Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological ...profile of different clinical severity are lacking. Methods. We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-without-ARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile. Results. Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations. Conclusions. The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death.
Increasing consumption of nitrofurantoin (NIT) for treatment of acute uncomplicated urinary tract infections (UTI) highlights the need to monitor emerging NIT resistance mechanisms. This study ...investigated the molecular epidemiology of the multidrug-resistant efflux gene oqxAB and its contribution to nitrofurantoin resistance by using Escherichia coli isolates originating from patients with UTI (n = 205; collected in 2004 to 2013) and food-producing animals (n = 136; collected in 2012 to 2013) in Hong Kong. The oqxAB gene was highly prevalent among NIT-intermediate (11.5% to 45.5%) and -resistant (39.2% to 65.5%) isolates but rare (0% to 1.7%) among NIT-susceptible (NIT-S) isolates. In our isolates, the oqxAB gene was associated with IS26 and was carried by plasmids of diverse replicon types. Multilocus sequence typing revealed that the clones of oqxAB-positive E. coli were diverse. The combination of oqxAB and nfsA mutations was found to be sufficient for high-level NIT resistance. Curing of oqxAB-carrying plasmids from 20 NIT-intermediate/resistant UTI isolates markedly reduced the geometric mean MIC of NIT from 168.9 μg/ml to 34.3 μg/ml. In the plasmid-cured variants, 20% (1/5) of isolates with nfsA mutations were NIT-S, while 80% (12/15) of isolates without nfsA mutations were NIT-S (P = 0.015). The presence of plasmid-based oqxAB increased the mutation prevention concentration of NIT from 128 μg/ml to 256 μg/ml and facilitated the development of clinically important levels of nitrofurantoin resistance. In conclusion, plasmid-mediated oqxAB is an important nitrofurantoin resistance mechanism. There is a great need to monitor the dissemination of this transferable multidrug-resistant efflux pump.
Peroxiredoxins are multifunctional enzymes that play a key role in protecting cells from stresses and maintaining the homeostasis of many cellular processes. Peroxiredoxins were firstly identified as ...antioxidant enzymes that can be found in all living organisms. Later studies demonstrated that peroxiredoxins also act as redox signaling regulators, chaperones, and proinflammatory factors and play important roles in oxidative defense, redox signaling, protein folding, cycle cell progression, DNA integrity, inflammation, and carcinogenesis. The versatility of peroxiredoxins is mainly based on their unique active center cysteine with a wide range of redox states and the ability to switch between low- and high-molecular-weight species for regulating their peroxidase and chaperone activities. Understanding the molecular mechanisms of peroxiredoxin in these processes will allow the development of new approaches to enhance longevity and to treat various cancers. In this article, we briefly review the history of peroxiredoxins, summarize recent advances in our understanding of peroxiredoxins in aging- and cancer-related biological processes, and discuss the future perspectives of using peroxiredoxins in disease diagnostics and treatments.
Trimethylamine-N-oxide (TMAO) is a risk factor for atherosclerosis. We compared the potency of fish oil with flaxseed oil in reducing TMAO-exacerbated atherogenesis. Five groups of ApoE–/– mice were ...given one of five diets, namely, a low-fat diet, a Western high fat diet (WD), a WD plus 0.2% TMAO, and two WDs containing 0.2% TMAO with 50% lard being replaced by flaxseed oil or fish oil. TMAO accelerated atherosclerosis and disturbed cholesterol homeostasis. Compared with flaxseed oil, fish oil was more effective in inhibiting TMAO-induced atherogenesis by lowering plasma cholesterol and inflammatory cytokines. Both oils could reverse TMAO-induced decrease in fecal acidic sterols. Fish oil promoted fecal output of neutral sterols and downregulated hepatic cholesterol biosynthesis. Fish oil was more effective than flaxseed oil in promoting the growth of short-chain fatty acid-producing bacteria and lowering microbial generation of lipopolysaccharide. In conclusion, fish oil is more potent than flaxseed oil to ameliorate TMAO-exacerbated atherogenesis.
Abstract
Background
Depression is a major public health concern. Emerging research has shown that cognitive behavioral therapy for insomnia (CBT-I) is effective in treating individuals with comorbid ...insomnia and depression. Traditional face-to-face CBT-I encounters many obstacles related to feasibility, accessibility, and help-seeking stigma. CBT-I delivered via smartphone application could be a potential solution. This paper reports a protocol designed to evaluate the efficacy of a self-help smartphone-based CBT-I, using a waitlist group as control, for people with major depression and insomnia.
Methods
A two-arm parallel randomized controlled trial is conducted in a target sample of 285 non-suicidal Hong Kong Chinese older than 17 years of age with major depression and insomnia. Participants complete an online rapid screening, followed by a telephone diagnostic interview. Those who meet the eligibility criteria are randomized in a ratio of 1:1 to receive either CBT-I immediately or to a waitlist control condition. The CBT-I consists of six weekly modules and is delivered through a smartphone application proACT-S. This smartphone app has been pilot tested and revamped to improve user experience. An online randomized algorithm is used to perform randomization to ensure allocation concealment. The primary outcomes are changes over the measurement points in sleep quality, insomnia severity, and depression severity. The secondary outcomes include changes over the measurement points in anxiety, subjective health, treatment expectancy, and acceptability of treatment. Assessments are administered at baseline, post-intervention, and 6-week follow-up. The recruitment is completed. Important adverse events, if any, are documented. Multilevel linear mixed model based on intention-to-treat principle will be conducted to examine the efficacy of the CBT-I intervention.
Discussion
It is expected that proACT-S is an efficacious brief sleep-focused self-help treatment for people with major depression and insomnia. If proven efficacious, due to its self-help nature, proACT-S may be applicable as a community-based early intervention, thereby reducing the burden of the public healthcare system in Hong Kong.
Trial registration
ClinicalTrials.gov
NCT04228146
. Retrospectively registered on 14 January 2020.
Background
Social distancing under the COVID‐19 pandemic has restricted access to community services for older adults with neurocognitive disorder (NCD) and their caregivers. Telehealth is a viable ...alternative to face‐to‐face service delivery. Telephone calls alone, however, may be insufficient. Here, we evaluated whether supplementary telehealth via video‐conferencing platforms could bring additional benefits to care‐recipient with NCD and their spousal caregivers at home.
Method
Sixty older adults NCD‐and‐caregiver dyads were recruited through an activity centre. The impact of additional services delivered to both care‐recipient and caregiver through video conference (n=30) was compared with telehealth targeted at caregivers by telephone only (n=30), over 4 weeks in a pretest‐posttest design. Interviews and questionnaires were conducted at baseline and study’s end.
Result
Supplementary telemedicine had averted the deterioration in the Montreal Cognitive Assessment evident in the telephone‐only group (ηp2=0.50). It also reversed the falling trend in quality of life observed in the telephone only group (QoL‐AD, ηp2=0.23). Varying degrees of improvements in physical and mental health (Short‐Form 36 v2), perceived burden (Zarit Burden Interview Scale) and self‐efficacy (Revised Caregiving Self‐Efficacy Scale) were observed among caregivers in the video‐conferencing group, which were absent in the telephone‐only group (ηp2=0.23–0.51).
Conclusion
Telehealth by video conference was associated with improved resilience and wellbeing to both people with NCD and their caregivers at home. The benefits were visible already after 4 weeks and unmatched by telephone alone. Video conference as the modus operandi of telehealth beyond the context of pandemic‐related social distancing should be considered.
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