Low-dose benzo[a]pyrene exposure induces hepatic lipid deposition through LCMT1/PP2Ac-mediated autophagy inhibition.

Non-alcoholic fatty liver disease (NAFLD) is a progressive disorder of liver metabolism and has become the most common chronic liver disease worldwide. Benzo[a]pyrene (BaP) is recognized as a potent carcinogen, but the effect of low-dose BaP on the development of NAFLD has not been well-studied, and its molecular mechanism is still unknown. In this study, we demonstrated that low-dose BaP induced hepatic steatosis in a mouse model with a notable increase in hepatic lipid content. Interestingly, mRNA expression of genes related to fatty acids uptake or synthesis was not significantly altered after BaP exposure. Instead, we found that low-dose BaP promoted lipid deposition in primary mouse hepatocytes by inhibiting autophagy, which was regulated through Leucine carboxyl methyltransferase-1 (LCMT1) mediated Protein Phosphatases 2A subunit C (PP2Ac) methylation. The role of LCMT1 in BaP-induced steatosis was further validated in a liver-specific lcmt1 knockout (L-LCMT1 KO) mouse model. In this study, we provided evidence to support a novel mechanism by which BaP induces the development of hepatic steatosis through PP2Ac mediated autophagy inhibition. These findings provided new insight into the pathogenesis of NAFLD induced by environmental exposure to low-dose BaP.

Hepatic leucine carboxyl methyltransferase 1 (LCMT1) contributes to high fat diet-induced glucose intolerance through regulation of glycogen metabolism.

Impaired glucose regulation is one of the most important risk factors for type 2 diabetes mellitus (T2DM) and cardiovascular diseases, which have become a major public health issue worldwide. Dysregulation of carbohydrate metabolism in liver has been shown to play a critical role in the development of glucose intolerance but the molecular mechanism has not yet been fully understood. In this study, we investigated the role of hepatic LCMT1 in the regulation of glucose homeostasis using a liver-specific LCMT1 knockout mouse model. The hepatocyte-specific deletion of LCMT1 significantly upregulated the hepatic glycogen synthesis and glycogen accumulation in liver. We found that the liver-specific knockout of LCMT1 improved high fat diet-induced glucose intolerance and insulin resistance. Consistently, the high fat diet-induced downregulation of glucokinase (GCK) and other important glycogen synthesis genes were reversed in LCMT1 knockout liver. In addition, the expression of GCK was significantly upregulated in MIHA cells treated with siRNA targeting LCMT1 and improved glycogen synthesis. In this study, we provided evidences to support the role of hepatic LCMT1 in the development of glucose intolerance induced by high fat diet and demonstrated that inhibiting LCMT1 could be a novel therapeutic strategy for the treatment of glucose metabolism disorders.

Wiltse transforaminal thoracic interbody fusion approach for the treatment of single­segment thoracic spinal tuberculosis in elderly patients with osteoporosis: A retrospective study of 20 cases.

The aim of the present study was to investigate the clinical feasibility and efficacy of the Wiltse approach and TTIF in elderly patients with single-segment thoracic tuberculosis (SSTTB) complicated with osteoporosis and neurological dysfunction. Between January 2017 and January 2019, 20 elderly patients underwent the Wiltse TTIF approach at a single hospital. The follow-up time of these patients was 37.15±7.37 months (range, 24-48 months). The preoperative kyphosis angle was 35.41±6.71˚. The degree of neurological deficit in each patient was assessed using the Frankel spinal cord injury classification. In addition, TB activity was monitored using erythrocyte sedimentation rate and C-reactive protein levels, and the degree of osteoporosis was evaluated using femoral neck bone mineral density T-scores. The 20 patients with SSTTB were completely cured without recurrence. The postoperative kyphotic angle was 8.80±0.79˚, without significant loss of correction at the final follow-up. Bone graft fusion was observed within 6-9 months, with all patients reporting relief of their back pain. The neurological condition of all the patients improved postoperatively. The present study indicates that Wiltse TTIF surgery combined with anti-TB chemotherapy has satisfactory efficacy in elderly patients with SSTTB complicated by osteoporosis and neurological impairment.

LCMT1 indicates poor prognosis and is essential for cell proliferation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most malignant type of cancers. Leuci carboxyl methyltransferase 1 (LCMT1) is a protein methyltransferase that plays an improtant regulatory role in both normal and cancer cells. The aim of this study is to evaluate the expression pattern and clinical significance of LCMT1 in HCC. METHODS: The expression pattern and clinical relevance of LCMT1 were determined using the Gene Expression Omnibus (GEO) database, the Cancer Genome Atlas (TCGA) program, and our datasets. Gain-of-function and loss-of-function studies were employed to investigate the cellular functions of LCMT1 in vitro and in vivo. Quantitative real-time polymerase chain reaction (RT-PCR) analysis, western blotting, enzymatic assay, and high-performance liquid chromatography were applied to reveal the underlying molecular functions of LCMT1. RESULTS: LCMT1 was upregulated in human HCC tissues, which correlated with a "poor" prognosis. The siRNA-mediated knockdown of LCMT1 inhibited glycolysis, promoted mitochondrial dysfunction, and increased intracellular pyruvate levels by upregulating the expression of alani-neglyoxylate and serine-pyruvate aminotransferase (AGXT). The overexpression of LCMT1 showed the opposite results. Silencing LCMT1 inhibited the proliferation of HCC cells in vitro and reduced the growth of tumor xenografts in mice. Mechanistically, the effect of LCMT1 on the proliferation of HCC cells was partially dependent on PP2A. CONCLUSIONS: Our data revealed a novel role of LCMT1 in the proliferation of HCC cells. In addition, we provided novel insights into the effects of glycolysis-related pathways on the LCMT1regulated progression of HCC, suggesting LCMT1 as a novel therapeutic target for HCC therapy.

Analysis of Clinical Characteristics of 556 Spinal Tuberculosis Patients in Two Tertiary Teaching Hospitals in Guangxi Province.

Spinal tuberculosis (STB), which accounts for half of musculoskeletal tuberculosis, is among the leading causes of extrapulmonary tuberculosis. Guangxi Province, located in southern China, is among the most severely affected provinces in China. In this study, we collected and analyzed data from 2 Class-A tertiary teaching hospitals in Nanning City, Guangxi Province, from 2011 to 2019, with the aim of providing reference points for the prevention, diagnosis, treatment, and prognosis analysis of STB, using the epidemiological characteristics of 556 STB cases. Our results revealed that males had a slightly higher incidence (50.17%) compared to females (49.83%), with 64.93% of cases falling between the ages of 18 and 45 years. Cases from rural communities accounted for 63.49% of the reviewed cases. The average time between onset of symptoms and hospitalization was 18.0 months (range: 1 day-220 months). The most commonly reported symptoms were lower back pain (78.60%), radicular pain (51.98%), and systemic toxemia (43.53%). Additionally, 53.98% of the reviewed cases had varying degrees of neurological impairment. The main pathological lesion locations were the lumbar spine (43.53%) and thoracic spine (32.55%). Among them, 72.66% of cases involved at least 2 vertebral segments, and 62.77% of cases presented with paravertebral abscesses. Among the cases reviewed, 90.65% underwent antituberculosis chemotherapy prior to surgery. Following treatment, the cure rate was 78.41%, while 3.78% of patients had postoperative relapse. There were cases of concomitant illnesses among the cases reviewed, 40.65% of patients also had pulmonary tuberculosis, 15.29% had hepatitis B, 13.30% had diabetes, and 7.91% had hypertension. Our results still demonstrate that spinal tuberculosis remains a serious public health problem in Guangxi Province. Thus, preventive measures should be directed towards rural residents with comorbidities such as the elderly and diabetic.