Maltol inhibits the progression of osteoarthritis via the nuclear factor-erythroid 2-related factor-2/heme oxygenase-1 signal pathway in vitro and in vivo.

Osteoarthritis (OA) is a common degenerative joint disease characterized by articular cartilage degeneration and inflammation. Currently, there is hardly any effective treatment for OA due to its complicated pathology and the severe side effects of the treatment drugs used. It has been reported that maltol, a Maillard reaction product derived from ginseng, inhibits inflammation and oxidative stress in several animal models. However, the potential anti-inflammatory effects of maltol in OA treatment are unknown. This study aimed to evaluate the anti-inflammatory effects of maltol on interleukin (IL)-1ß-induced mouse chondrocytes and protective effects of maltol on these chondrocytes in medial meniscus destabilization (DMM) OA mouse models. Mice, randomly divided into maltol (n = 15), vehicle (n = 15) and control (n = 15) groups were treated with the same dose of maltol or saline, respectively. The cartilage tissues were extracted for histological analysis 8 weeks postoperative. For the in vitro studies, chondrocytes were treated with 10 ng mL-1 IL-1ß combined with maltol at different concentrations. In vitro assays showed that the maltol pre-treatment significantly inhibited the expressions of multiple inflammatory factors induced by IL-1ß, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α). In addition, maltol alleviated the degradation of the extracellular matrix (ECM) by inhibiting the expressions of matrix metalloproteinase-13 (MMP13) and thrombospondin motif 5 (ADAMTS5), as well as reversing the degradation of aggrecan and collagen II. Moreover, maltol suppressed nuclear factor kappa B (NF-κB) signaling by activating the nuclear factor-erythroid 2-related factor-2 (Nrf2) in in vitro and in vivo studies. These findings indicate that maltol reduces the inflammation induced by IL-1ß in chondrocytes. Therefore, the results of this study indicated that maltol may be a potential drug for the effective treatment of OA.

Association of an Exon SNP of SLC2A9 Gene with Hyperuricemia Complicated with Type 2 Diabetes Mellitus in the Chinese Male Han Population.

Several recent genome-wide association studies and following studies have identified that genetic variants of SLC2A9 are associated with hyperuricemia (HUA) and diabetes mellitus (DM). Here, we set to investigate whether the exon 9 of SLC2A9 gene variations is associated with HUA complicated with Type 2 DM (T2DM) in the Chinese male Han population. The present study was designed to study rs2280205 polymorphism in exon 9 of SLC2A9 in 232 Chinese male subjects. Rs2280205 locus was genotyped in 52 T2DM subjects, 65 HUA subjects, 55 subjects with HUA complicated with T2DM, as well as 60 control subjects in this study. DNA from peripheral blood was purified and amplified by polymerase chain reaction (PCR). The PCR products were then digested by restriction enzyme MSPI, and part of PCR products was sequenced and analyzed. There was no significant difference in the levels of cholesterol, creatinine, and urea nitrogen between the Control Group and the HUA group. There was also no significant difference in levels of cholesterol between the DM group and Control Group. No significant difference in cholesterol and uric acid was observed between the HUA group and the HUA accompanied with DM group (P > 0.05). However, there was no statistical significance in the genotype frequency in these groups (P > 0.01). Results of the present study suggest that the exon 9 of SLC2A9 gene 109C/T polymorphism is not associated with HUA and diabetes in population living in the coastal area of Shandong province, China.

1,4-Bis(thio-phen-2-yl)butane-1,4-dione.

In the centrosymmetric title compound, C(12)H(10)O(2)S(2), the alkyl chains adopt a fully extended all-trans conformation with respect to the C(thio-phene)-C bond. The non-H atoms of the mol-ecule are nearly planar, with a maximum deviation of 0.063 (2) Šfrom the mean plane of the constituent atoms. In the crystal, symmetry-related mol-ecules are linked via pairs of C-H⋯π contacts [H-centroid distances of the thio-phene units = 2.79 (9) and 2.82 (4) Å], in turn inter-digitating with each other along the bc plane, thus leading to an inter-woven two-dimensional network.

Identification of a novel mutation in a pseudohypoparathyroidism family.

Pseudohypoparathyroidism type Ia (PHP Ia) is defined as a series of disorders characterized by multihormone resistance in end-organs and Albright hereditary osteodystrophy (AHO) phenotype. PHP Ia is caused by heterozygous inactivating mutations in GNAS, which encodes the stimulatory G-protein alpha subunit (Gsa). A patient with typical clinical manifestations of pseudohypoparathyroidism (PHP) (round face, short stature, centripetal obesity, brachydactyly, and multi-hormone resistance: parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), and gonadotropins) presented at our center. The sequence of the GNAS gene from the patient and her families revealed a novel missense mutation (Y318H) in the proband and her mother. An in vitro Gsa functional study showed that Gsa function was significantly impaired. These results stress the importance of GNAS gene investigation.

[Association of the exon 8 and intron 8 polymorphisms of the human urate transporter 1 gene with primary hyperuricemia in Chinese Han population].

OBJECTIVE: To investigate the association of the exon 8 and intron 8 polymorphisms of the human urate transporter 1 gene SLC22A12 with primary hyperuricemia (HUA) in Chinese Han population. METHODS: Genomic DNA from 215 individuals with HUA and 323 controls was extracted. The exon 8 and intron 8 of the SLC22A12 gene was amplified by polymerase chain reaction (PCR). PCR product was sequenced directly. Single nucleotide polymorphisms (SNPs) were detected and the association of the SNPs with primary HUA was assessed. RESULTS: (1) Two SNPs were identified, they were T1309C located in exon 8 (rs7932775) and -103A to G located in intron 8. Pairwise linkage disequilibrium analysis displayed an absolute linkage disequilibrium between the two SNPs (D'= 1). (2) The minor allele frequencies for both SNPs were 51.9% in HUA patients, which were significantly different from that of controls (42.4%)(P< 0.01). (3) The genotype frequencies of GG+ GA and CC+ CT in HUA patients were significantly higher than that in controls (80.0% vs. 69.0%, P< 0.01). (4) Individuals of both GG+ GA and CC+ CT genotypes had 1.79 fold increase of HUA risk (OR= 1.794, 95%CI: 1.19-2.70). CONCLUSION: These findings indicated that T1309C and -103A to G polymorphisms of the SLC22A12 gene were associated with primary HUA in Chinese Han population.

[Anti-inflammatory action of lipid-bound apoA-I cysteine mutants].

OBJECTIVE: To determine the anti-inflammatory functions of different cysteine mutants of apolipoprotein A-I recombinant HDLs. METHODS: The recombinant HDLs (named rHDL52, rHDL107, rHDL173, rHDLwt) were reconstituted by mixing wild types or their mutants with dipalmitoyl phosphatidylcholine. And the in vivo effects on lipopolysaccharide (LPS)-induced endotoxemia were examined in mice. The plasma levels of plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in by ELISA were tested. And we also set up two control groups: LPS and saline. RESULTS: The rHDL52 mice had a significant decrease of plasma TNF-alpha and IL-1beta and the protection of lung against acute injury. 24 h post-injection as compared with rHDLwt group [TNF-alpha: (135.28 +/- 12.84) pg/ml, IL-1beta: (82.00 +/- 8.19) pg/ml], the rHDL52 mice exhibited a higher capability of lowering the plasma levels of TNF-alpha and IL-1beta [(39.66 +/- 2.44) pg/ml, (66.83 +/- 6.24) pg/ml, both P < 0.05]. And, as indicated by histological sections of lung tissue, the rHDL52 mice could also lower the infiltration of inflammatory cells in lung. CONCLUSION: rHDL52 has a higher anti-inflammation capability than wild type rHDLwt.

NALP3 inflammasome functional polymorphisms and gout susceptibility.

Gout is the most common autoinflammatory arthritis characterized by elevated serum urate and recurrent attacks of intra-articular crystal deposition of monosodium urate (MSU). Although the pathogenesis of gout is still unclear, accumulated studies indicate that genetic factors trigger gout development, including some susceptibility genes that control the production and clearance of urate and lead to hyperuricemia. However, the epidemiological evidence suggests that only less than 10% of hyperuricemia patients develop gout, indicating that other genes unrelated to the urate metabolism may also contribute to the diseases susceptibility. Accumulated evidences have implied that MSU crystal-induced inflammation is a paradigm of innate immunity and that NALP3 inflammasome, an innate immune complex containing NALP3, ASC and CARD-8, is involved in gout development. Recent studies suggest that NALP3 and CARD-8 functional mutations contribute to the development of autoinflammatory diseases including hereditary periodic fever syndrome, arthritis as well as hypertension susceptibility. Taking into account these genetic findings, here we would like to propose a novel hypothesis that functional mutations in NALP3 inflammasome may make NALP3 inflammasome as attractive susceptibility candidates and genetic markers for gout. Further clinical genetic studies need to be performed to confirm the role of NALP3 inflammasome in the etiology of gout.

[Effect of lipid-bound apoA-I cysteine mutants upon lipopolysaccharide-induced endotoxemia in mice].

OBJECTIVE: To determine the anti-inflammatory functions of different cysteine mutants of apolipoprotein A-I recombinant HDLs. METHODS: The authors reconstituted recombinant HDLs (namely rHDL74, rHDL129, rHDL195 and rHDL228) by mixing wild type or those mutants with dipalmitoyl phosphatidylcholine and examined their in vivo effects upon LPS-induced endotoxemia in mice. RESULTS: At 24 h post-injection, mice receiving rHDL74 [TNF-alpha: (24 +/- 3) pg/ml; IL-1beta: (45 +/- 5) pg/ml] had a significant decrease of plasma tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) as compared with control mice receiving either saline or rHDLwt [TNF-alpha: (135 +/- 12) pg/ml; IL-1beta: (82 +/- 8) pg/ml, P < 0.05]. Administration of rHDL74 to mice injected with LPS also led to a protection of lung against acute injury and attenuation of endotoxin-induced clinical symptoms in mice as compared with controls injected with LPS only. CONCLUSION: Compared with rHDLwt, rHDL74 exhibits higher anti-inflammation capabilities. And it may be a potential clinical candidate for therapy for endotoxin-induced septic shock.

[Research Progress of microRNAs and human hematological diseases - review].

The microRNAs (miRNAs) are an evolutionarily conserved class of 22 nucleotide (19 - 25 nt) non-coding RNAs. The miRNAs are partially complementary to 3' untranslated region of target mRNA, resulting in the repression of gene expression at post-transcriptional level. The miRNAs have been associated with diverse biological processes. This review summarizes recent progress of research on the characteristics and function of miRNAs, and the role of miRNAs in hematological malignancy development.