HDAC1 overexpression promoted by METTL3-IGF2BP2 inhibits FGF21 expression in metabolic syndrome-related liver injury.

Metabolic syndrome (MetS) represents a cluster of diseases that includes diabetes and insulin resistance. A combination of these metabolic disorders damages liver function. We hypothesized here that histone deacetylase 1 (HDAC1) inhibits fibroblast growth factor 21 (FGF21) expression through histone deacetylation, thereby accentuating liver injury in rats with MetS. MetS rats induced by a high-fat diet were monitored weekly for blood pressure and body weight measurement. The changes of hepatic injury parameters were also measured. The pathological changes in the liver were observed by HE staining and oil red O staining. We found that HDAC1 was increased in the liver of rats with MetS, while sh-HDAC1 reduced blood pressure, body weight, and hepatic injury parameters. Improvement of structural pathological alterations and reduction of lipid deposition were observed after HDAC1 inhibition. Notably, HDAC1 inhibited FGF21 expression through histone deacetylation. The hepatoprotective effects of sh-HDAC1 on rats were reversed by adenovirus-mediated knockdown of FGF21. Moreover, methyltransferase-like 3 (METTL3) mediated the N6-methyladenosine (m6A) modification of HDAC1 mRNA and increased its binding to IGF2BP2. Consistently, sh-METTL3 inhibited HDAC1 and increased FGF21 expression, thereby ameliorating liver injury in MetS rats. This study discovered that HDAC1 is capable of managing liver injury in MetS. Targeting HDAC1 may be an optimal treatment for MetS-related liver injury.

Pyogenic liver abscess complicated with endogenous endophthalmitis caused by Klebsiella pneumoniae: A case report and Literature Review.

OBJECTIVE: Pyogenic liver abscess (PLA) is a common surgical infectious disease caused by various pathogens. Klebsiella pneumoniae is a relatively recent cause, often affecting patients with low immunity. Endogenous endophthalmitis (EE), a rare and serious complication of PLA, may appear with eye symptoms before PLA. By reviewing a case of Klebsiella pneumoniae-induced PLA complicated with EE, we want to summarize the information about the characteristics, causes, and complications of PLA based on the literature review. METHODS: This case report describes a 37-year-old male who had fever high to 39°C for 10 days experienced blurred vision followed by nonlight perception vision. He reported a history of diabetes irregularly taking oral medications and insulin therapy. Imaging examination found a large low-density area in the right lobe of the liver with an unclear border and vague surrounding fat gap. The blood culture was not positive. The culture of the drainage fluid from the liver puncture showed Klebsiella pneumonia. Blood and liver puncture drainage fluid were sent for microbial high-throughput gene detection with next-generation sequencing technology (NGS), which confirmed the diagnosis of Klebsiella pneumoniae-induced PLA complicated with EE. RESULTS: The patient's surgical incision had healed well at discharge, and he could feel light at his left eye. But the patient was lost to follow-up since the third month after discharge. CONCLUSION: By reviewing this case and summarize the information about the characteristics, causes, and complications of PLA based on the literature review, we concluded that it is necessary to promptly perform liver puncture drainage and empirically use antibiotics for patients with PLA, especially those with poor glycemic control, to avoid serious complications such as EE.

Correlations of cardiovascular autonomic neuropathy with urinary albumin excretion rate and cardiac function in patients with type 2 diabetes mellitus.

BACKGROUND: The associations of cardiovascular autonomic neuropathy (CAN) with diabetic nephropathy and heart disease remain elusive. The aim of this study was to explore the correlations of CAN with urinary albumin excretion rate (UAER) and cardiac function in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 225 T2DM patients were assigned into CAN and non-CAN groups using cardiovascular reflex tests (CARTs). They were divided into macroalbuminuria, microalbuminuria and normoalbuminuria groups according to urinary albumin/creatinine ratio (UACR), or left ventricular diastolic dysfunction and normal groups based on left ventricular peak E/A velocity ratio (E/A). The correlations of CAN with albuminuria and left ventricular diastolic dysfunction, and the predictive values of UACR and E/A were analyzed. RESULTS: Compared with non-CAN group, CAN group had older age, longer T2DM duration, higher serum urine acid (SUA) level, UACR, systolic and diastolic pressure differences between supine and standing positions, and lower other CARTs parameters and E/A (P<0.001). Macroalbuminuria group had largest positional systolic and diastolic pressure differences, and lowest other CARTs parameters (P<0.001). Compared with normal group, left ventricular diastolic dysfunction group had larger positional systolic and diastolic pressure differences, and lower other CARTs parameters (P<0.001). CAN in T2DM patients was positively correlated with albuminuria and left ventricular diastolic dysfunction (P<0.001). Age, SUA, UACR and E/A were independent predictive factors (P=0.031, 0.005, <0.001, <0.001). UACR and E/A had high predictive values. CONCLUSIONS: In T2DM patients, CAN is positively correlated with declined UAER and cardiac function. UACR and E/A have high predictive values.