Perirenal Fat Thickness is Associated with Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes Mellitus.

Objective: Recent advances in perirenal adipose tissue (PAT) highlighted that PAT might involve in the pathogenesis of chronic inflammatory and dysfunctional metabolic diseases. This study assessed the association between perirenal fat thickness (PrFT) and metabolic dysfunction-associated fatty liver disease (MALFD) in type 2 diabetes mellitus (T2DM). Methods: This study comprised 867 eligible participants with T2DM. Trained reviewers collected anthropometric and biochemical measurements. The diagnosis of MAFLD was based on the latest international expert consensus statement. PrFT and fatty liver were evaluated by computed tomography. The visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by bioelectrical impedance analysis. The non-alcoholic fatty liver disease fibrosis score (NFS) and fibrosis-4 (FIB-4) index were used to assess progressive liver fibrosis in MAFLD. Results: Overall, the prevalence of MAFLD was 62.3% in T2DM. The PrFT in the MAFLD group was statistically increased than in the non-MAFLD group (P < 0.05). Correlation analysis showed that PrFT was significantly correlated with dysfunctional metabolic factors like body mass index, waist circumference, triglycerides, high-density lipoprotein cholesterol, systolic blood pressure, diastolic blood pressure, uric acid, and insulin resistance. Multiple regression analysis revealed that PrFT was positively correlated with NFS (ß=0.146, P<0.001) and FIB-4 (ß=0.082, P=0.025) in the MAFLD. In contrast, PrFT was negatively correlated with CTL-S (ß=-0.188, P<0.001). Furthermore, PrFT was also significantly associated with MAFLD independent of VFA and SFA, the OR (95% CI) was 1.279 (1.191-1.374). Meanwhile, PrFT also had a good identifying value for MAFLD as VFA. The area under the curve (95% CI) value of PrFT identifying MAFLD was 0.782 (0.751-0.812). The optimal cut-off value of PrFT was 12.6mm, with a sensitivity of 77.8% and specificity of 70.8%. Conclusion: PrFT was independently associated with MAFLD, NFS, and FIB-4 and showed a similar identifying value for MAFLD as VFA, which suggested that PrFT can be used as an alternative index to VFA.

MTNR1B polymorphisms with CDKN2A and MGMT methylation status are associated with poor prognosis of colorectal cancer in Taiwan.

BACKGROUND: Identifying novel colorectal cancer (CRC) prognostic biomarkers is crucial to helping clinicians make appropriate therapy decisions. Melatonin plays a major role in managing the circadian rhythm and exerts oncostatic effects on different kinds of tumours. AIM: To explore the relationship between MTNR1B single-nucleotide polymorphism (SNPs) combined with gene hypermethylation and CRC prognosis. METHODS: A total of 94 CRC tumour tissues were investigated. Genotyping for the four MTNR1B SNPs (rs1387153, rs2166706, rs10830963, and rs1447352) was performed using multiplex polymerase chain reaction. The relationships between the MTNR1B SNPs and CRC 5-year overall survival (OS) was assessed by calculating hazard ratios with 95%CIs. RESULTS: All SNPs (rs1387153, rs2166706, rs10830963, and rs1447352) were correlated with decreased 5-year OS. In stratified analysis, rs1387153, rs10830963, and rs1447352 risk genotype combined with CDKN2A and MGMT methylation status were associated with 5-year OS. A strong cumulative effect of the four polymorphisms on CRC prognosis was observed. Four haplotypes of MTNR1B SNPs were also associated with the 5-year OS. MTNR1B SNPs combined with CDKN2A and MGMT gene methylation status could be used to predict shorter CRC survival. CONCLUSION: The novel genetic biomarkers combined with epigenetic biomarkers may be predictive tool for CRC prognosis and thus could be used to individualise treatment for patients with CRC.

Epidemiologic Characteristics of Domestic Patients with Hemorrhagic Fever with Renal Syndrome in Taiwan: A 19-Year Retrospective Study.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is an illness caused by hantaviruses. Numerous factors modify the risk of hantavirus transmission. This study explored the epidemiological characteristics, differences, and trends in terms of gender, age, season, and living areas of those diagnosed with domestically acquired HFRS in Taiwan from 2001 to 2019. METHODS: We examined publicly available annual summary data on the domestic cases with HFRS from 2001 to 2019; these data were obtained from the web database of Taiwan's Centers for Disease Control (CDC). RESULTS: This study analyzed 21 domestic cases with HFRS from Taiwan's CDC databases. In this study of the cases of HFRS in Taiwan, a gradual increase in the cases of those aged ≥40 years acquiring the disease was noted, and a distinct pattern of seasonal variation (spring) was observed. Furthermore, more men had domestically acquired HFRS, and living in Taipei metropolitan area (6 cases [28.6%]) and the rural areas (Gao-Ping region, 9 cases [42.9%]) was identified as a potential risk factor. This study represents the first report of confirmed cases of domestically acquired HFRS from surveillance data from Taiwan's CDC, 2001-2019. CONCLUSION: This study highlights the importance of longitudinal studies covering a wide geographical area, particularly for highly fluctuating pathogens, to understanding the implications of the transmission of zoonotic diseases in human populations. Important data were identified to inform future surveillance and research efforts in Taiwan.

Heme oxygenase-1 aggravates heat stress-induced neuronal injury and decreases autophagy in cerebellar Purkinje cells of rats.

We previously reported that heat stroke induces autophagy as a protection mechanism against neurodegeneration in the brain. Heme oxygenase (HO)-1 is a stress protein and can be induced by heat stress (HS). Cerebellar Purkinje cells are selectively vulnerable to heat-induced injury. In this study, we first validated an animal model of HS (38°C for 4 h) in which sustained increase of Purkinje cell injury, HO-1 expression up to 24 h post HS (HS24), and hyperthermia reaching a rectal temperature 41.52 ± 0.32 were observed. In subsequent experiments, we investigated the effects of HO-1 on HS-induced Purkinje cell injury. Rats were divided into four groups: one normothermic control group receiving saline vehicle (1 mL/kg, intraperitoneal [i.p.]) and exposed to 25 for 4 h; and three HS groups receiving saline, or HO-1 inducer haemin (30 mg/kg, i.p.) or HO-1 inhibitor tin protoporphyrin (SnPP, 30 mg/kg, i.p.), respectively, at 12 h prior to HS. HS-induced Purkinje cell injury was further enhanced by HO-1 inducer but attenuated by HO-1 inhibitor as evaluated by immunoreactivity of apoptosis marker (active caspase-3) as well as Fluoro-Jade B histochemistry (staining for degenerating neurons), suggesting a detrimental role of HO-1. Interestingly, the protective autophagy was reduced by HO-1 inducer but enhanced by HO-1 inhibitor as demonstrated by autophagy markers including Beclin-1 and microtubule-associated protein light chain 3 in Purkinje cells. Double immunofluorescent labelling of Beclin-1 or 8-hydroxydeoxyguanosine (an oxidative DNA damage marker) with HO-1 immunoreactivity not only demonstrated their co-localization, but also confirmed that HO-1 negatively regulated Beclin-1 but increased oxidative stress in the same Purkinje cell. Taken together, our results indicate that HO-1 aggravates HS injury in cerebellar Purkinje cells. Our findings shed new light on cell damage mechanisms by HS in central nervous system and may help to provide potential therapeutic foci.

Heat stroke induces autophagy as a protection mechanism against neurodegeneration in the brain.

Heat stroke (HS) is defined clinically as a condition when core body temperature rises above 40°C and is accompanied by central nervous system abnormalities. In this study, we established a rat model of HS by exposing anesthetized rats to elevated ambient temperature (40°C) until core temperature reaching 40.5°C (HS onset). The rat was immediately removed from heating chamber, allowed recovery for various time periods, and killed for histological and biochemical studies. Our results indicated neuronal shrinkage and pyknosis of the nucleus and sustained up to 12 h recovery time in cerebral cortex. Elevated expression of autophagy-related proteins, including microtubule associated protein light chain 3 and beclin 1 in cortical tissue at various times (3, 6, 12 h) of recovery was observed. In addition, the number of autophagosomes stained by monodansylcadaverine, a specific autophagosome marker, increased after heat exposure but was reduced by pretreatment with 3-methyladenine, an autophagy inhibitor. Furthermore, heat exposure increased neuronal degeneration in cortical tissue, as evidenced by staining with the fluorescent dye Fluoro-Jade B for degenerating neuron. Pretreatment with 3-methyladenine in HS rats aggravated neurodegeneration. Taken together, these results suggest that HS induces autophagy as a protection mechanism against neurodegeneration. Modulation of autophagy may provide a potential therapeutic approach for HS and await further research.