Purpose:To investigate the status of p16 gene and its influence in p16 mRNA expression in primary hepatocellular carcinoma (HCC). Methods:The methylation status of p16 gene and expression of p16 mRNA were examined by methylation-specific PCR (MSP) and RT-PCR in twenty-five primary HCC and corresponding paracancerous tissue specimens.Results:Methylation was detected in 12 of 25 (52.0%) tumor tissue specinmens, while 6 of 25 (24.0%) in corresponding paracancerous tissue specimens. Loss of p16 mRNA expression was found in 19 specimens with methylated p16 gene,while expression of p16 mRNA was detected in 27 of 31 specimens with unmethylated p16 gene. There was significant difference in mRNA expression between specimens with methylated p16 and unmethylated p16.Conclusions:p16 gene methylation is a frequent event in HCC. The methylation of p16 gene might lead to loss of p16 mRNA expression. Detection of p16 gene methylation may be a useful marker in the molecular diagnosis of hepatocellular carcinomas.

The effects of pioglitazone on the expressions of hypoxia-inducible factor-1 α (HIF-1 α) and vascular endothelial growth factor (VEGF) in renal tissues of diabetic rats were observed. Diabetic rat model was established by feeding high-carbonhydrate-fat diet and injecting streptozotocin. After the treatment with pioglitazone, the kidney index, 24 h urinary albumin, blood urea nitrogen, serum creatinine, fasting blood glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), total cholesterol,triglycerides, and low-density lipoprotein-cholesterol of diabetic rats were significantly lower than those of untreated ones, high-density lipoprotein-cholesterol was increased, the expressions of HIF-1α and VEGF in renal tissue were decreased ( all P＜0. 01 ). It suggested that pioglitazone may improve renal function and the balance of glucose-lipid metabolism in diabetic rats via down-regulating HIF-1/VEGF pathway.

Objective To investigate the protective effect of quercetin on diabetic nephropathy and to explore its possible mechanism.Methods Type 2 diabetes mellitus rat model was established by feeding high-carbonhydrate-fat diet and injecting with streptozotocin.At 72 hour after injection,blood samples were collected from the tail veins of all rats.Those rats with blood glucose level ≥ 16.7 mmol/L were considered as the diabetes model been successfully established.The model rats were randomly divided into type 2 diabetic group ( group DM,n =9 ) and quercetin group ( group QUE,n =9 ).Other rats were used as normal controls (group NC,n =8).All rats were performed by intragastric administration for 8 weeks.At the end of experiment,the rats were sacrificed and fasting plasma glucose( FPG),fasting insulin( Flns),serum creatinine (SCr),blood urea nitrogen(BUN),TG,TC,LDL-C,24 h urine protein (24 h UP),and kidney index ( KI ) were evaluated.Pathological changes of kidney were observed by periodic acid-silver metheramine( PASM ).The expressions of ubiquitin and NF-κB p65 on glomeruli w ere examined by immunohistochemical method,and its association with the incidence of proteinuria was analyzed.Results In groups DM and QUE,the level of FPG [ ( 25.45 ± 1.23 ) mmol/L and ( 19.99 ± 1.20 ) mmoL/L],FIns [ ( 25.67 ± 2.58 ) mU/L and ( 19.29 ± 1.80 ) mU/L ],SCr[ ( 44.00 ± 2.53 ) μmol/L and ( 34.43 ± 2.23 )μmol/L],BUN[ ( 11.60 ± 0.39 )mmol/L and (8.20 ± 0.37) mmoL/L],TG [ (3.32 ± 0.22 ) mmol/L and (2.43±0.25)mmol/L],TC[(2.95 ±0.21) mmol/L and (2.24 ±0.17)mmol/L],LDL-C[(2.03 ±0.22 ) mmol/L and ( 1.49 ± 0.13 ) mmol/L ],24 h UP [ ( 46.67 ± 2.50 ) mg/24 h and ( 25.57 ± 2.82 )mg/24 h]and KI[ (9.76 ±0.30) × 103 and (8.44 ±0.26) × 103 ] were significantly increased than the indexes of group NC [ (6.56 ± 0.41 ) mmol/L,( 12.63 ± 1.41 ) mU/L,( 22.88 ± 2.36 ) μmol/L,( 5.45 ±0.51 ) mmoL/L,( 1.64 ± 0.1 1 ) mmol/L,( 1.33 ± 0.17 ) mmol/L,(0.46 ± 0.05 ) mmol/L,( 12.38 ±1.19)/24 h and (6.78 ±0.12) × 103].Moreover,the above indexes in group QUE were obviously lower than group DM.There was evidence of pathological changes associated with diabetes,such as focal and segmental sclerosis and thickened basement and mesangial expansion.The expressions of ubiquitin and NF-κB p65 in renal tissues of group DM increased significantly ( P ＜ 0.01 ).The expression of ubiquitin and NF-κB p65 were positively related with the level of 24 h UP ( r =0.893,0.879,P ＜ 0.01 ).Compared with group DM,all above indexes in group QUE were markedly alleviated ( P ＜ 0.01 ).The expression of ubiquitin and NF-κB p65 was reduced but didn't reach level in group NC ( P ＜ 0.01 ).Conclusion The increased expression of NF-κB induced by ubiquitin-proteasome system may participate in the pathogenesis of proteinuria in diabetic nephropathy.Quercetin has renal protective effects partly through reducing NF-κB p65 expression.

  Objective  To summarize the clinical manifestations, pathological features and gene mutation diversity of Blau syndrome/early-onset sarcoidosis.  Methods  We collected general data, clinical manifestations, and auxiliary examination results from 8 patients who were diagnosed of Blau syndrome/early-onset sarcoidosis and treated in our hospital from January 2011 to December 2022, and then summarized and analyzed their characteristics and diversity.  Results  Among the 8 patients, 4 were males and 4 were females. The onset age was 3 to 8 months old. Rash was the first symptom in 7 patients(87.5%). 6 patients(75.0%) had papules and erythema.3 cases(37.5%) had arthritis. 2 cases(25.0%) had uveitis and other eye inflammation. 4 cases (50.0%) also showed intermittent fever. 3 cases (37.5%) showed symptoms in nerve and respiratory system, and hypertension respectively. The skin histopathology of 8 patients showed non-caseous granuloma formation. In laboratory detection, CRP and TNF-α were significantly increased before treatment, while IL-6, IL-8, TNF-α and IL-2 receptor(IL-2R) were significantly decreased in 5 patients after glucocorticoid therapy. The results of genetic testing showed that 4 of the 7 patients had p.R334W(c.1000C > T) mutation, 1 had p.H313R(c.938A > G) and p.R471C(c.1411C > T)double mutation, and 1 had p.476_477del (c.1427_1429delcct).  Conclusions  Blau syndrome/early-onset sarcoidosis has significant features in clinical manifestations, histopathology and gene mutation, but it also has diversity.

Exosomes are cell-derived nanovesicles with diameters from 30 to 150 nm, released upon fusion of multivesicular bodies with the cell surface. They can transport nucleic acids, proteins, and lipids for intercellular communication and activate signaling pathways in target cells. In cancers, exosomes may participate in growth and metastasis of tumors by regulating the immune response, blocking the epithelial-mesenchymal transition, and promoting angiogenesis. They are also involved in the development of resistance to chemotherapeutic drugs. Exosomes in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of cancers. Because of their amphipathic structure, exosomes are natural drug delivery vehicles for cancer therapy.

Gangliosides are a class of important glycosphingolipids containing sialic acid that are widely distributed on the outer surface of cells and are abundantly distributed in brain tissue. Disialoganglioside with three glycosyl groups (GD3) and disialoganglioside with two glycosyl groups (GD2) are markedly increased in pathological conditions such as cancers and neurodegenerative diseases. GD3 and GD2 were found to play important roles in cancers by mediating cell proliferation, migration, invasion, adhesion, angiogenesis and in preventing immunosuppression of tumors. GD3 synthase (GD3S) is the regulatory enzyme of GD3 and GD2 synthesis, and is important in tumorigenesis and the development of cancers. The study of GD3S as a drug target may be of great significance for the discovery of new drugs for cancer treatment. This review will describe the gangliosides and their roles in physiological and pathological conditions; the roles of GD3 and GD2 in cancers; the expression, functions and mechanisms of GD3S, and its potential as a drug target in cancers.

Glioblastoma is the most common and aggressive primary tumor in the central nervous system, accounting for 12%-15% of all brain tumors. 3--Acetyl-11-keto--boswellic acid (AKBA), one of the most active ingredients of gum resin from Birdw., was reported to inhibit the growth of glioblastoma cells and subcutaneous glioblastoma. However, whether AKBA has antitumor effects on orthotopic glioblastoma and the underlying mechanisms are still unclear. An orthotopic mouse model was used to evaluate the anti-glioblastoma effects of AKBA. The effects of AKBA on tumor growth were evaluated using MRI. The effects on the alteration of metabolic landscape were detected by MALDI-MSI. The underlying mechanisms of autophagy reducing by AKBA treatment were determined by immunoblotting and immunofluorescence, respectively. Transmission electron microscope was used to check morphology of cells treated by AKBA. Our results showed that AKBA (100 mg/kg) significantly inhibited the growth of orthotopic U87-MG gliomas. Results from MALDI-MSI showed that AKBA improved the metabolic profile of mice with glioblastoma, while immunoblot assays revealed that AKBA suppressed the expression of ATG5, p62, LC3B, p-ERK/ERK, and P53, and increased the ratio of p-mTOR/mTOR. Taken together, these results suggested that the antitumor effects of AKBA were related to the normalization of aberrant metabolism in the glioblastoma and the inhibition of autophagy. AKBA could be a promising chemotherapy drug for glioblastoma.

Glioblastoma multiforme (GBM) in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it. Studies of sinomenine, an alkaloid from the Chinese medicinal plant,