Novel discovery of schisandrin A regulating the interplay of autophagy and apoptosis in oligoasthenospermia by targeting SCF/c-kit and TRPV1 via biosensors.

Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10-15 g/L, and the quantitative limit reached 1.0 × 10-13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (KD) of 5.701 × 10-11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a KD of up to 4.181 × 10-10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.

[Critical quality attribute characterization of big brand TCM: taste formulation optimization strategy and application of Xiaoer Ganmao Oral Liquid based on taste quality attribute].

The taste is the quality attribute for the development and production of traditional Chinese medicine(TCM). To improve the medication compliance of the big brand TCM, Xiaoer Ganmao Oral Liquid, a correlation model between the electronic tongue sensor signal value and human sensory evaluation score was established, and an optimization strategy of taste improvement for Xiaoer Ganmao Oral Liquid was developed with the key techniques of statistical experimental design. Based on the above model, the optimal formulation was determined as follows: aspartame content of 1-2 mg·mL~(-1), acesulfame-K content of 1.5-3 mg·mL~(-1), and steviol glycoside content of 1-2 mg·mL~(-1). Furthermore, the optimal formulation was verified by human sensory evaluation. Therefore, the taste of Xiaoer Ganmao Oral Liquid was improved. Taking Xiaoer Ganmao Oral Liquid as an example, the present study developed the taste formulation optimization method based on the correlation between the electronic tongue and human sensory evaluation, which is expected to provide an important reference to improve the taste of oral liquid of TCM.

Metabolomic profiling and alleviation of oxidative stress of Huangjing Zanyu capsule treating oligoasthenospermia.

Background: The traditional Chinese medicine (TCM) patent medicine Huangjing Zanyu capsule (HJZY capsule) has achieved satisfactory clinical effects in the treatment of oligoasthenospermia (OAS). This study aimed to elucidate the impact of HJZY capsule on the reproductive system, focusing on oxidative stress and metabolism profiling during the intervention, to clarify the therapeutic mechanism of HJZY capsule in treating OAS. Methods: Cyclophosphamide was used to establish OAS model rats. Time-sequence specimen collection was applied to monitor the dynamic development of the pharmacological effect of HJZY capsule. Superoxide dismutase (SOD), glutathione peroxidase (GPX), and malonaldehyde (MDA) were evaluated by biochemistry kits to examine the impact of HJZY capsule on oxidative stress. Non-targeted metabolomics was conducted for urine and testis samples, respectively, to investigate metabolic pathways through which the HJZY capsule takes effect. Results: The HJZY capsule elevated sperm density from 62.1±8.28, passing 68.4±7.52, to 75.9±8.48×106/mL, and sperm motility from 62.0%±3.94%, passing 70.8%±9.72%, to 68.8%±4.37%. Meanwhile, SOD (P<0.05 in week 2) and GPX activity levels of HJZY groups were elevated to a certain degree, respectively, and lipid oxidation was attenuated, as shown by decreased MDA content (P<0.05 in week 2). Metabolomics results showed that the HJZY capsule could modulate pathways including taurine metabolism, purine and pyrimidine metabolism, glycerolipid and glycerophospholipid metabolism, and multiple amino acid metabolisms, among others. The cluster analysis results showed that urinary and testicular metabolomics differed in the strength of discrimination between rats in the OAS model and the HJZY groups. Conclusions: The HJZY capsule exerts a comprehensive effect on OAS through influencing various metabolic pathways. Non-targeted metabolomics provides an effective way for profiling complex TCM prescriptions.

[Case series analysis of Professor Wang Qi's prescriptions for oligoasthenospermia].

OBJECTIVE: To conduct a case series analysis on Professor Wang Qi's prescriptions for oligoasthenospermia and a preliminary discussion on the clinical application of the pathogenesis theory of "kidney deficiency with dampness, heat, stasis, toxin and parasites" so as to provide some reference for the diagnosis and treatment of oligoasthenospermia by traditional Chinese medicine (TCM). METHODS: We selected 13 representative cases of oligoasthenospermia treated by Professor Wang Qi, analyzed the basic conditions of the patients, changes of the disease and prescriptions used, and investigated the treatment of oligoasthenospermia in view of Professor Wang Qi's TCM theory on andrology. RESULTS: Excellent therapeutic effect was achieved in 7, indefinite effect in 5 and no effect in 1 of the 13 cases. Totally 38 prescriptions were employed in the treatment, of which Bajitian was used in 30, Tusizi in 27, Gouqizi in 25, Sangshen in 25, Shuizhi in 24 and Danggui in 22. The drugs used in the treatment of 10 or more patients included Bajitian in 12, Sangshen in 11, Shuizhi in 11, Tusizi in 10 and Gouqizi in 10 cases. CONCLUSIONS: Professor Wang Qi's prescriptions are effective for the treatment of oligoasthenospermia and the pathogenesis theory of "kidney deficiency with dampness, heat, stasis, toxin and parasites" is valuable in guiding the clinical diagnosis and treatment in traditional Chinese medicine.

Fate of Mercury in Volatiles and Char during in Situ Gasification Chemical-Looping Combustion of Coal.

Mercury emission is an important issue during in-situ gasification chemical-looping combustion ( iG-CLC) of coal. This work focused on experimentally "isolating" two elementary subprocesses (coal pyrolysis and char gasification) during iG-CLC of coal, identifying mercury distribution within the two subprocesses, and examining the effects of a hematite oxygen carrier (OC) on the mercury fate. The mercury measurement accuracy was carefully ensured by comparing online measurements (by a VM 3000 instrument) and benchmark measurements (by the standard Ontario Hydro Method, ASTM D6784) as well as repeated tests (10 times for each case). The mercury mass balance was 115% for the entire iG-CLC. A total of 44.7% of the mercury was released as the gas phase form within the coal pyrolysis process at a typical CLC operation temperature (950 °C), whereas 13.4% was released during the char gasification process. The release rate and amount of mercury were minimally affected by the presence of OC; however, the OC promoted the conversion of Hg0(g) to Hg2+(g). Only a small amount of mercury was absorbed by the OC and transported into the air reactor along with carbon residue, released as Hg0(g) and Hg2+(g) or remained in the OC and coal ash as particulate mercury.

[Huatan Qushi Decoction improves lipid metabolism and semen quality in obese rats with oligoasthenozoospermia: Effects and mechanisms].

OBJECTIVE: To explore the regulatory effect of Huatan Qushi Decoction (HTQSD) on lipid metabolism and semen quality in obese rats with oligoasthenozoospermia (OA) and its underlying mechanisms. METHODS: Ninety-six 8-week-old male Wistar rats were randomly divided into six groups of equal number: blank control, OA model control, Wuzi Yanzong Pills (WZYZP), and high-, medium- and low-dose HTQSD, the blank controls fed with a normal diet and the others with a high-fat diet, all for 8 weeks. Meanwhile, the rats in the blank control and OA model control groups were treated intragastrically with normal saline, those in the WZYZP group with WZYZP at 1.07 g/kg, and those in the high-, medium- and low-dose HTQSD groups with HTQSD at 26.25, 13.125 and 6.5625 g/kg, respectively. The body weights of the animals were obtained at 1, 4 and 8 weeks of modeling and intervention, the levels of serum TG, TC, HDL-C and LDL-C, the liver and testis indexes and semen quality detected at 4 and 8 weeks, and the expression of HO-1 mRNA determined at 8 weeks. RESULTS: At 8 weeks of modeling and intervention, the rats in the model control group, compared with the blank controls, showed significant increases in the body weight (ï¼»523.1 ± 25.54ï¼½ vs ï¼»451.50 ± 27.53ï¼½ g, P < 0.01) and levels of serum TG (ï¼»8.58 ± 0.39ï¼½ vs ï¼»2.18 ± 0.28ï¼½ nmol/L, P < 0.001), TC (ï¼»4.41 ± 1.44ï¼½ vs ï¼»1.68 ± 0.18ï¼½ nmol/L, P < 0.01) and LDL-C (ï¼»2.06 ± 0.17ï¼½ vs ï¼»0.48 ± 0.57ï¼½ nmol/L,P<0.01), but decreases in the level of serum HDL-C (ï¼»27.92 ± 0.40ï¼½ vs ï¼»57.47 ± 1.52ï¼½ nmol/L,P < 0.01), sperm motility (ï¼»11.31 ± 4.87ï¼½% vs ï¼»39.66 ± 2.77ï¼½%, P < 0.01), sperm concentration (ï¼»31.07 ± 10.52ï¼½ vs ï¼»65.37 ± 6.30ï¼½ ×106/ml, P < 0.01) and the expression of HO-1 mRNA (0.16 ± 0.03 vs 1.06 ± 0.20, P < 0.01). The rats in the medium-dose HTQSD group, in comparison with the model controls, exhibited remarkable decreases in the body weight (ï¼»445.13 ± 34.19ï¼½ vs ï¼»523.1 ± 25.54ï¼½ g, P < 0.01) and levels of serum TG (ï¼»2.05 ± 0.27ï¼½ vs ï¼»8.58 ± 0.39ï¼½ nmol/L,P < 0.01), TC (ï¼»1.63 ± 0.21ï¼½ vs ï¼»4.41 ± 1.44ï¼½ nmol/L,P < 0.01) and LDL-C (0.45 ± 0.07) vs ï¼»2.06 ± 0.17ï¼½ nmol/L, P < 0.01), but increases in the level of serum HDL-C (ï¼»48.35 ± 3.63ï¼½ vs ï¼»27.92 ± 0.40ï¼½ nmol/L, P < 0.01), sperm motility (ï¼»32.84 ± 6.22ï¼½% vs ï¼»11.31 ± 4.877ï¼½%, P < 0.01) and sperm concentration (ï¼»46.90 ± 6.39ï¼½ vs ï¼»31.07 ± 10.52ï¼½ ×106/ml, P < 0.05), and the low-dose HTQSD group showed a significantly up-regulated expression of HO-1 mRNA (0.76 ± 0.13 vs 0.16±0.03, P < 0.01). CONCLUSIONS: HTQSD can regulate the blood lipid level and improve semen quality in obese rats with oligoasthenozoospermia by promoting serum anti-oxidation and reducing oxidative stress.