Research progress of targeted therapy regulating Th17/Treg balance in bone immune diseases.

Rheumatoid arthritis (RA) and postmenopausal osteoporosis (PMOP) are common bone-immune diseases. The imbalance between helper (Th17) and regulatory T cells (Tregs) produced during differentiation of CD4+ T cells plays a key regulatory role in bone remodelling disorders in RA and PMOP. However, the specific regulatory mechanism of this imbalance in bone remodelling in RA and PMOP has not been clarified. Identifying the regulatory mechanism underlying the Th17/Treg imbalance in RA and PMOP during bone remodelling represents a key factor in the research and development of new drugs for bone immune diseases. In this review, the potential roles of Th17, Treg, and Th17/Treg imbalance in regulating bone remodelling in RA and PMOP have been summarised, and the potential mechanisms by which probiotics, traditional Chinese medicine compounds, and monomers maintain bone remodelling by regulating the Th17/Treg balance are expounded. The maintenance of Th17/Treg balance could be considered as an therapeutic alternative for the treatment of RA and PMOP. This study also summarizes the advantages and disadvantages of conventional treatments and the quality of life and rehabilitation of patients with RA and PMOP. The findings presented her will provide a better understanding of the close relationship between bone immunity and bone remodelling in chronic bone diseases and new ideas for future research, prevention, and treatment of bone immune diseases.

Early-onset COQ8B (ADCK4) glomerulopathy in a child with isolated proteinuria: a case report and literature review.

BACKGROUND: Herein, a 3-year-old boy presented with hidden-onset isolated proteinuria was reported. The disease was induced by COQ8B (previously termed ADCK4) compound heterozygous variants, including c.[271C > T] and c.[737G > A], which were inherited from his father and mother, respectively. CASE PRESENTATION: The patient visited our clinic due to non-nephrotic range proteinuria for 3 months, but no obvious abnormality was detected in the vital signs or laboratory test results. Renal histopathology revealed mitochondrial nephropathy, which manifested as mild glomerular abnormalities under light microscope, together with mitochondrial proliferation and hypertrophy and crowded arrangement under electron microscope. As suggested by whole exome sequencing, the patient inherited the COQ8B compound heterozygous variants from both of his parents who showed normal phenotype. After literature review, it was confirmed that one of the variant site (c.[271C > T]) had not been reported among the East Asian populations so far. CONCLUSIONS: Steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis are the most common phenotypes and renal histopathological manifestations of COQ8B variant. Nonetheless, our case shows that such variant may have hidden and mild clinical manifestations at the early onset. Therefore, early diagnosis will help to identify children at the early disease stage who have opportunity to benefit from oral coenzyme Q10 supplementation.

Biological evaluation of a novel Herceptin-platinum (II) conjugate for efficient and cancer cell specific delivery.

Platinum-based drugs have been widely used for the treatment of malignant tumors. However, their applications are limited by severe side effects for their lack of selectivity for cancer cells. The development of antibody drug conjugates (ADCs) have provided a platform to reduce drug toxicity and improve drug efficacy. Here we describe a nover conjugate comprising of Herceptin (an anti-HER2 antibody) and platinum drug via a cathepsin B cleavable dipetide for enhancing drug accumulation and HER2-positive cancer cell specific delivery. This conjugate is believed to be cleaved by cathepsin B, leading to a 1,6-elimination reaction and activation of drug release. Herceptin-Pt(II) is evaluated to have approximately loaded with 6.4 moles platinum drugs per mole of antibody. We demonstrate that Herceptin-Pt(II) retain high and selective binding affinity for HER2 protein and HER2-positive SK-BR-3 cancer cells. The in vitro cytotoxicity tests indicate that Herceptin-Pt(II) exhibits much higher cytotoxicity than oxaliplatin against SK-BR-3 cells. More importantly, Herceptin-Pt(II) shows no obvious inhibition against the growth of both MCF-7 and MDA-MB-231 cells, which express lower levels of HER2. Furthermore, compared with free oxaliplatin, Herceptin significantly improved the cellular uptake of platinum drugs in SK-BR-3 cells. In summary, Herceptin-platinum (II) conjugate is a remarkable and potent platform for efficient and cancer cell specific delivery.

Fluoride removal mechanism of bayerite/boehmite nanocomposites: roles of the surface hydroxyl groups and the nitrate anions.

Three-dimensional feather like bayerite/boehmite nanocomposites were synthesized by a facile one-pot hydrothermal method. The obtained nanocomposites were characterized by X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, and nitrogen adsorption-desorption isotherms. The removal properties toward fluoride were investigated, including adsorption kinetics, adsorption isotherm, and influences of pH and coexisting anions. The maximal adsorption capacity was 56.80 mg g(-1) at pH 7.0, which is favorable compared to those reported in the literature using other adsorbents. The coexisting of sulfate and bicarbonate inhibited the fluoride removal especially at high concentrations. Furthermore, the removal mechanism was revealed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The results suggest that both of the surface hydroxyl groups and the nitrate anions were participated in the ion-exchange process.

Enzymatic preparation of 20(S, R)-protopanaxadiol by transformation of 20(S, R)-Rg3 from black ginseng.

20(S)-protopanaxadiol (PPD(S)) and 20(R)-protopanaxadiol (PPD(R)), the main metabolites of ginsenosides Rg3(S) and Rg3(R) in black ginseng, are potential candidates for anti-cancer therapy due to their pharmacological activities such as anti-tumor properties. In the present study, we report the preparation of PPD(S, R) by a combination of steaming and biotransformation treatments from ginseng. Aspergillus niger was isolated from soil and showed a strong ability to transform Rg3(S, R) into PPD(S, R) with 100% conversion. Furthermore, the enzymatic reactions were analyzed by reversed-phase HPLC, showing the biotransformation pathways: Rg3(S)-->Rh2(S)-->PPD(S) and Rg3(R)-->Rh2(R)-->PPD(R), respectively. In addition, 12 ginsenosides including 3 pairs of epimers, namely Rg3(S), Rg3(R), Rh2(S), Rh2(R), PPD(S) and PPD(R), were simultaneously determined by reversed-phase HPLC. Our study may be highly applicable for the preparation of PPD(S) and PPD(R) for medicinal purposes and also for commercial use.

Simultaneous quantification of 19 ginsenosides in black ginseng developed from Panax ginseng by HPLC-ELSD.

A high-performance liquid chromatographic method with evaporative light scattering detection (HPLC-ELSD) has been developed to identify and quantify 19 ginsenosides (Rg(1), Re, Rf, Rb(1), Rc, Rb(2), Rd, F(4), Rg(6), Rk(3), Rh(4), 20(S)-, 20(R)-Rg(3), 20(S)-, 20(R)-Rs(3), Rk(1), Rg(5), Rs(4), and Rs(5)) in black ginseng (BG, Korean white ginseng that was subjected to nine cycles of steam treatment). Ultrasonication is employed for sample preparation, and the analysis is achieved on a Discovery C(18) column using gradient elution of CH(3)CN-H(2)O-CH(3)COOH without buffer in 40min. The method was validated by linearity (r(2)> or =0.9994), precision (92.0-107.5%), intra- and inter-day accuracy (R.S.D.<3.21%), and limit of detection (LOD< or =93ng). The quantification method was applied to analyze the composition of ginsenosides in Korean white, red, and black ginsengs. During the preparatory process of BG, ginsenosides transform into constituents of low polarity by hydrolysis, isomerization, and dehydration at C-20, and hydrolysis also occurs at C-3 or C-6. The validated HPLC method is expected to provide the basis for the quality assessment of ginseng products.

[Cortical neuron apoptosis induced by beta-amyloid peptide and protective effect of panoxadiol in mice].

OBJECTIVE: To investigate the apoptosis of cortical neurons induced by beta-amyloid peptide (Abeta(1-40)) and the protective effect of panoxadiol. METHODS: The Abeta(1-40) induced damage of primarily cultured mouse cortical neurons was examined with morphological observation, MTT assay, DNA agarose gel electrophoresis and Western-blot. RESULT: After 48 h treated with 12 mumol/L Abeta(1-40), the cortical neurons showed apoptotic characteristics: including decreased OD570 value in MTT assay, DNA cleavage fragment in electrophoresis and increased apoptotic cells. Western-blot showed that the expression of bcl-2 reduced significantly (P<0.05). Cell apoptosis was significantly attenuated in 40 mg/L panoxadiol treated group. CONCLUSION: Panoxadiol can protect cultured cortical neurons from apoptosis induced by Abeta(1-40) in mice.

Optimization of ginsenosides hydrolyzing beta-glucosidase production from Aspergillus niger using response surface methodology.

To optimize ginsenosides hydrolyzing beta-glucosidase production from Aspergillus niger, response surface methodology was carried out in two stages. The Plackett-Burman design was achieved to screen the important variables that influence beta-glucosidase production. Among 10 variables (wheat bran, soybean powder, CaCl(2), ginsenosides, KH(2)PO(4), MgSO(4), polyethylene glycol (PEG), medium volume, inoculum size, and stirring speed), it was found that wheat bran, KH(2)PO(4), and stirring speed had significant effect on beta-glucosidase activity due to very low p-values (p<0.05). Subsequently, wheat bran, KH(2)PO(4), and stirring speed were further optimized using central composite design. The optimal beta-glucosidase production was predicted to be 4650.14 U/ml with the combination of factors (wheat bran, 34.51 g/l; KH(2)PO(4), 1.78 g/l; stirring speed, 161.60 rpm/min). Finally, under optimal fermentation conditions, ginsenoside Rb(1) was converted to Rd and F(2) by A. niger within 10 min. Little compound K was detected at 30 min, and finally F(2) was completely transformed to compound K within 8 h. The putative conversion pathway of Rb(1) by A. niger was Rb(1), Rd, F(2), and compound K.

Effects of choleretics on bile compositions drained from patients with pigment gallstone.

OBJECTIVE: To provide evidence for three-level prevention of cholelithiasis by means of observing the effects of some choleretics on bile compositions drained from patients with pigment gallstone. METHODS: Twenty-seven patients suffering from primary pigment gallstones and having received treatment of choledochostomies plus T-tube or endoscopic nasal bile drainage (ENBD) were divided equally into three groups, and administered respectively with Lidanling (the LDL group), ursodesoxycholic acid (the UDA group) and combination of LDL and UDA (the LDL + UDA group) through oral intake (7 patients in each group). Besides, 6 post-operational patients got no treatment with any drug were allocated in the control group. Bile of all the patients was collected before treatment and on the 1, 3, 5, 7 th day after the treatment started to detect levels of total bile acid (TBA), glycocholic acid (GCA), taurocholic acid (TCA), glycocholic cheno-desoxycholic acid (GCDCA), total bilirubin (TBIL), uncombined bilirubin (UCB), concentration of calcium ion (Ca(2+)) as well as the bacterio-genetic and endogenous beta-glucuronidase activity for comparing. RESULTS: Levels of TBA, GCA, TCA and GCDCA got gradually increased in the UDA group and the LDL + UDA group after treatment (P < 0.05), while those in the LDL group remained unchanged, showing an insignificant difference as compared with those in the control group. In the LDL group and the LDL + UDA group, TBIL gradually increased while UCB gradually decreased in the course of treatment (P < 0.05). Moreover, levels of Ca(2+) and endogenous beta-glucuronidase activity got significantly lowered (P < 0.05). CONCLUSION: Combined use of LDL and UDA could elevate levels of TBA, GCA, TCA, GCDCA, enhance the excretion of TBIL in patients with pigment gallstone after bile drainage, lower levels of UCB and Ca(2+) and the activity of endogenous beta-glucuronidase in the bile, so as to reduce the possibility of stone formation of bile, and therefore, it could be used to prevent the production of pigment gallstone, especially to prevent post-operative recurrence of stones.