Enhancement effect of l-cysteine on lactic acid fermentation production.

BACKGROUND: Environmental stress resistance is still a bottleneck for economical process for l-lactic acid fermentation. Chronological lifespan (CLS) extension has represented a promising strategy for improving stress resistance of microbial cell factories. MAIN METHODS AND MAJOR RESULTS: In this study, addition of anti-aging drug cysteine, a kind of extending CLS of microbial cell factories, was systematically evaluated on cell viability and l-lactic acid production in Bacillus coagulans CICC 23843. The results revealed that 16 mm l-cysteine supplement significantly improved l-lactic acid titer in B. coagulans. The enhanced total antioxidant capacity (T-AOC) and key enzymes activities involving in glycolytic pathway as well as differentially expressed genes involved in cysteine synthesize and cysteine precursor synthesize pathways, and fatty acid degradation pathway may help to further understand the relative mechanism of l-cysteine effect on improving l-lactic acid accumulation. Finally, based on 16 mm l-cysteine supplement, a final l-lactic acid titer of 130.5 g L-1 with l-lactic acid productivity of 4.07 g L-1  h-1 and the conversion rate of 0.94 g g-1 total sugar was achieved in a 5 L bioreactor. CONCLUSIONS AND IMPLICATIONS: This study provided a valuable option for engineering lactic acid bacteria lifespan for enhancement of lactic acid yield.

Modulation of the autonomic nervous system by one session of spinal low-level laser therapy in patients with chronic colonic motility dysfunction.

Patients with a defecation disorder may not evoke a normal defecation reflex, or the reflex may be excessive, as a dysfunction of the spinal autonomic nervous system. Treatment with various forms of lumbar and sacral neuromodulation have shown symptom improvement, but potential changes in autonomic functioning are rarely studied. Here we evaluate the effects on autonomic function of a single session of low-level laser therapy (LLLT) on the lumbar and sacral spine in 41 patients with chronic gastrointestinal motor dysfunction. The LLLT protocol used red LED light at a wavelength of 660 nm for 10 min and infrared LED light at a wavelength of 840 nm for 10 min, followed by infrared laser light at a wavelength of 825 nm for 10 min. Effects on the autonomic nervous system were assessed by measuring heart rate variability (HRV) changes. Respiratory Sinus Arrhythmia (RSA) and Root Mean Square of Successive Differences (RMSSD) were used to quantify parasympathetic reactivity; the Baevsky's Stress Index (SI) reflected sympathetic activity while the ratios SI/RSA and SI/RMSSD were used to show shifts in autonomic dominance. The results indicate that lumbar and sacral neuromodulation using light arrays reduced, whereas stimulation by the laser probes significantly increased parasympathetic activity. The light arrays increased whereas the laser probes significantly decreased sympathetic activity (SI). The entire protocol shifted the autonomic balance toward parasympathetic activity. The comparison of actual vs. sham neuromodulation proved that the change in HRV parameters was due to actual light stimulation and not due to the arrays and probe touching the skin. In conclusion, a single session of LLLT markedly affects autonomic nervous system activity reflected in changes in HRV which is only possible by generating activity in the spinal autonomic nerves. These results warrant a study into the effects of LLLT on restoring autonomic dysfunction in chronic refractory colonic motility disorders.

Oryzanol Attenuates High Fat and Cholesterol Diet-Induced Hyperlipidemia by Regulating the Gut Microbiome and Amino Acid Metabolism.

Hyperlipidemia is intricately associated with the dysregulation of gut microbiota and host metabolomes. This study explored the antihyperlipidemic function of oryzanol and investigated whether the function of oryzanol affected the gut microbiome and its related metabolites. Hamsters were fed a standard diet (Control) and a high fat and cholesterol (HFCD) diet with or without oryzanol, separately. Our results showed that oryzanol significantly decreased HFCD-induced fat accumulation, serum total cholesterol, low-density lipoprotein cholesterol (LDL-c), LDL-c/HDL-c ratio, triglyceride, and liver steatohepatitis, attenuated HFCD-induced gut microbiota alterations, and altered amino acid concentrations in feces and the liver. We investigated the role of the gut microbiota in the observed beneficial effects; the protective effects of oryzanol were partly diminished by suppressing the gut bacteria of hamsters after using antibiotics. A fecal microbiota transplantation experiment was carried out by transplanting the feces from HFCD group hamsters or hamsters given oryzanol supplementation (as a donor hamster). Our results showed that administering the fecal liquid from oryzanol-treated hamsters attenuated HFCD-induced hyperlipidemia, significantly decreased the abundance of norank_f__Erysipelotrichaceae, norank_f__Eubacteriaceae, and norank_f__Oscillospiraceae and the concentration of tyrosine. These outcomes are significantly positively correlated with serum lipid concentration. This study illustrated that gut microbiota is the target of oryzanol in the antihyperlipidemic effect.

Oryzanol alleviates high fat and cholesterol diet-induced hypercholesterolemia associated with the modulation of the gut microbiota in hamsters.

A high fat and cholesterol diet (HFCD) can modulate the gut microbiota, which is closely related with hypercholesterolemia. This study aimed to explore the anti-hypercholesterolemia effect of oryzanol, and investigate whether the function of oryzanol is associated with the gut microbiota and related metabolites. 16S rRNA and ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry were applied for the gut microbiota and untargeted metabolomics, respectively. The results showed that HFCD significantly upregulated body fat accumulation and serum lipids, including triglyceride, total cholesterol, low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), and ratio of LDL-c/HDL-c, which induced hypercholesterolemia. Oryzanol supplementation decreased body fat accumulation and serum lipids, especially the LDL-c concentration and LDL-c/HDL-c ratio. In addition, the abundances of Desulfovibrio, Colidextribacter, norank_f__Oscillospiraceae, unclassified_f__Erysipelotrichaceae, unclassified_f__Oscillospiraceae, norank_f__Peptococcaceae, Oscillibacter, Bilophila and Harryflintia were increased and the abundance of norank_f__Muribaculaceae was decreased in HFCD-induced hyperlipidemia hamsters. Metabolites were changed after HFCD treatment and 9 differential metabolites belonged to bile acids and 8 differential metabolites belonged to amino acids. Those genera and metabolites were significantly associated with serum lipids. HFCD also disrupted the intestinal barrier. Oryzanol supplementation reversed the changes of the gut microbiota and metabolites, and intestinal barrier injury was also partly relieved. This suggests that oryzanol supplementation modulating the gut microbiota contributes to its anti-hyperlipidemia function, especially anti-hypercholesterolemia.

Efficacy and Safety of Chinese Herbal Formula Granules in Treating Chronic Kidney Disease Stage 3: A Multicenter, Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

BACKGROUND: It is generally considered that traditional Chinese medicine (TCM) therapy postpones the progression of some chronic kidney diseases (CKDs). Chinese medicine herbs are widely applied in TCM therapy. We aimed to evaluate clinical efficacy and safety of Chinese herbal formula granules in patients with CKD stage 3 through a prospective randomized controlled study. METHODS: A total of 343 participants with CKD stage 3 were recruited from 9 hospitals in Jiangsu Province between April 2014 and October 2016. Participants were randomly assigned to a treatment or control group. Patients in the treatment group orally took Chinese herbal formula granules twice a day, while controls received placebo granules. The duration of intervention was 24 weeks. Primary outcomes were 24-hour proteinuria, serum creatinine, and eGFR, which were measured every 4 weeks. RESULTS: There was no statistical difference in 24-hour proteinuria between the two groups (0.97 ± 1.14 g/d vs. 0.97 ± 1.25 g/d). Patients in the treatment group had significantly lower serum creatinine level (130.78 ± 32.55 µmol/L versus 149.12 ± 41.27 µmol/L) and significantly higher eGFR level (55.74 ± 50.82 ml/min/1.73·m2 versus 44.46 ± 12.60 ml/min/1.73·m2) than those in the control group (P < 0.05). There was no significant difference between two groups in the incidence of adverse events. CONCLUSION: The treatment adopting Chinese herbal formula granules for 24 weeks improved kidney function of patients with CKD stage 3.

Data Mining-Based Analysis of Chinese Medicinal Herb Formulae in Chronic Kidney Disease Treatment.

BACKGROUND: Traditional Chinese medicine (TCM) has long been used to treat chronic kidney disease (CKD) in Asia. Its effectiveness and safety for CKD treatment have been confirmed in documented studies. However, the prescription rule of formulae for Chinese medicinal herbs is complicated and remains uncharacterized. Thus, we used data mining technology to evaluate the treatment principle and coprescription pattern of these formulae in CKD TCM treatment. METHODS: Data on patients with CKD were obtained from the outpatient system of a TCM hospital. We established a Chinese herb knowledge base based on the Chinese Pharmacopoeia and the Chinese Materia Medica. Then, following extraction of prescription information, we deweighted and standardized each prescribed herb according to the knowledge base to establish a database of CKD treatment formulae. We analyzed the frequency with which individual herbs were prescribed, as well as their properties, tastes, meridian tropisms, and categories. Then, we evaluated coprescription patterns and assessed medication rules by performing association rule learning, cluster analysis, and complex network analysis. RESULTS: We retrospectively analyzed 299 prescriptions of 166 patients with CKD receiving TCM treatment. The most frequently prescribed core herbs for CKD treatment were Rhizoma Dioscoreae (Shanyao), Spreading Hedyotis Herb (Baihuasheshecao), Root of Snow of June (Baimagu), Radix Astragali (Huangqi), Poria (Fulin), Rhizoma Atractylodis Macrocephalae (Baizhu), Radix Pseudostellariae (Taizishen), and Fructus Corni (Shanzhuyu). The TCM properties of the herbs were mainly being warm, mild, and cold. The tastes of the herbs were mainly sweet, followed by bitter. The main meridian tropisms were Spleen Meridian of Foot-Taiyin, Liver Meridian of Foot-Jueyi, Lung Meridian of Hand-Taiyin, Stomach Meridian of Foot-Yangming, and Kidney Meridian of Foot-Shaoyin. The top three categories were deficiency-tonifying, heat-clearing, and dampness-draining diuretic. CONCLUSION: Using an integrated analysis method, we confirmed that the primary TCM pathogeneses of kidney disease were deficiency and dampness-heat. The primary treatment principles were tonifying deficiency and eliminating dampness-heat.

Protection of Anthocyanin from Myrica rubra against Cerebral Ischemia-Reperfusion Injury via Modulation of the TLR4/NF-κB and NLRP3 Pathways.

Myrica rubra (MR) is rich in anthocyanins, and it has good anti-cancer, anti-aging, antioxidant, and antiviral effects. The proportion of disability and death caused by ischemic stroke gradually increased, becoming a major disease that is harmful to human health. However, research on effects of anthocyanin from MR on cerebral ischemia-reperfusion (I/R) injury is rare. In this study, we prepared eight purified anthocyanin extracts (PAEs) from different types of MR, and examined the amounts of total anthocyanin (TA) and cyanidin-3-O-glucoside (C-3-G). After one week of PAE treatment, the cerebral infarction volume, disease damage, and contents of nitric oxide and malondialdehyde were reduced, while the level of superoxide dismutase was increased in I/R mice. Altogether, our results show that Boqi¹ MR contained the most TA (22.07%) and C-3-G (21.28%), and that PAE isolated from Dongkui MR can protect the brain from I/R injury in mice, with the mechanism possibly related to the Toll-like receptor 4 (TLR4)/ nuclear factor-κB (NF-κB) and NOD-like receptor pyrin domain-containing 3 protein (NLRP3) pathways.

[Differential expressions of miRNAs in kidney in puromycin aminonucleoside nephropathy model and intervened effects of Leizhi capsule].

OBJECTIVE: To observe the differential expression characteristics of microRNAs (miRNAs) in renal tissues in puromycin aminonucleoside (PAN) nephritic model, and its relationship with key structural molecules of slid diaphragm (SD) nephrin and podocin and expression of skeleton protein synaptopodin; and to explore the in vivo mechanisms of Leizhi capsule (LZC) for ameliorating the expressions of nephrin, podocin and synaptopodin and reducing proteins by regulating the modal rat renal tissues miRNAs. METHOD: Fifty male Wistar rats were randomly divided into five groups: the control group (A), the model group (B), the LZC-treated group (C), the multi-glycoside of Tripterygium wilfordii (GTW)-treated group (D) and the valsartan-treated group (E). Apart from group A, all of rats in the remaining groups are injected with PAN (100 mg x kg(-1)) through jugular veins to establish the PAN nephropathy model. On the 2nd day after PAN nephropathy model was established, group C was orally administered with LZC (5 mL x kg(-1) x d(-1)) in group C, group DGTW (10 mL x kg(-1) x d(-1)), and E group valsartan (7.5 mL x kg(-1) x d(-1)), while groups A and B were intervened with physiological saline, for 10 days. Body weight and 24 h urinary protein ration (Upro) in all rats were measured at day 0, 3, and 9. All rats were sacrificed at day 11 after the establishment of the model, and their blood and renal tissues were collected to observe such blood biochemical indicators including albumin (Alb), serum creatinine (Scr), blood urea nitrogen (BUN) and glomerular ultrastructure (podocyte foot process form) and expressions of dicer enzyme, nephrin, podocin and synaptopodin in renal tissues. Meanwhile, the differential expressional characteristics of miRNAs in renal cortex were analyzed by biochip assay. Additionally, the differential expressional volumes of rno-miR-23a, rno-miR-300-3p, rno-miR-24 and rno-miR-30c were measured by real-time PCR. RESULT: Proteinuria, renal dysfunction, hypoproteinemia and podocyte foot process fusion were investigated in model rats induced by PAN. In renal tissues of PAN nephropathy model rats, dicer enzyme affected the expressions of nephrin, podocin and synaptopodin in podocytes, up-regulated the expressions of rno-miR-23a and rno-miR-300-3p, and down-regulated the expressions of rno-miR-24 and rno-miR-30c. The miRNAs with differential expressions included rno-miR-24, rno-miR-30c, rno-miR-23a and rno-miR-300-3p. LZC could improve the general state, proteinuria, serum BUN and podocyte foot process fusion of PAN nephropathy model rats, reduced the expressions of dicer enzyme, increased the expressions of nephrin, podocin and synaptopodin in podocytes, weakened the up-regulated rno-miR-23a and rno-miR-300-3p, and strengthened the down-regulated rno-miR-24 and rno-miR-30c in renal tissues. CONCLUSION: PAN in vivo impacts the expressions of miRNAs in renal tissues, intervenes the expressions of nephrin, podocin and synaptopodin in podocytes, damages podocyte structures and functions and generates proteinuria by means of differential expression of dicer enayme/miRNAs. LZC can reduce proteinuria in PAN nephropathy model rats. Its mechanism may intervene dicer enayme/miRNAs differential expression, regulate nephrin, podocin and synaptopodin in podocytes and improve podocyte structures and functions.

[Treatment of chronic primary glomerulopathy patients of Shen deficiency and dampness heat syndrome by yishen qingli granule combined low-dose Tripterygium wilfordii multiglycoside tablet: a clinical efficacy observation].

OBJECTIVE: To evaluate the clinical efficacy and safety of treatment of chronic primary glomerulopathy (CPG) patients of Shen deficiency and dampness heat syndrome (SDDHS) by Yishen Qingli Granule (YQG) combined with low-dose Tripterygium Wilfordii multiglycoside Tablet (TWT). METHODS: Totally 231 CPG patients of SDDHS were enrolled in this study (including 60 patients from First Affiliated Hospital of Nanjing University of Chinese Medicine, 58 from First Affiliated Hospital of Nanjing Medical University, 46 from Xinqiao Hospital of Third Military Medical University, 35 from First Affiliated Hospital of Guangzhou University of Chinese Medicine, 14 from First Affiliated Hospital of Soochow University, and 18 from Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine). They were randomly assigned to the control group (116 cases) and the trial group (115 cases) according to block group method. There were 217 cases in the safety analysis set (109 cases in the trial group vs 108 cases in the control group), and 203 cases in the full analysis set (99 cases in the trial group vs 104 cases in the control group). All patients received basic treatment such as ACEI/ARB. Furthermore, YQG (consisting of raw astragalus 10 g, prepared Polygonum Multiflorum 10 g, Pyrrosia 10 g, 1.5 g each package, containing 10 g of crude drugs) was additionally given to patients in the trial group, each package, twice daily. The TWT (10 mg) was given, twice a day. The TWT dose was adjusted according to 24 h urinary total protein (UTP). The placebos of YQG and TWT were administered to those in the control group. The treatment course consisted of 24 weeks and the follow-up visit lasted for 24 weeks. The biochemical indices were observed before and after treatment including 24 h UTP, urine red cell count (U(RBC)), renal functions (BUN, SCr), blood routine test (WBC), and liver functions (SGPT, SGOT). Reverse reactions such as gastrointestinal discomfort, skin rash, and irregular menstruation were also observed. RESULTS: Compared with the control group, the total effective rate was better in the trial group (82.83% vs 61.54%, P < 0.01). Results of stratified comparison of UTP showed better efficacy in the trial group (0.8-3.0 g/24 h, P < 0.01). The UTP decline occurred in the trial group after 8 weeks of treatment, with stable action, showing statistical difference when compared with the control group (P < 0.01). In the trial group, U(RBC) level decreased after treatment but changed more significantly. But there was no statistical difference in the changes when compared with the control group (P > 0.05). After treatment, there were no statistical difference in safety indicators such as WBC, SGPT, and SGOT between the two groups after treatment (P > 0.05). CONCLUSION: On the basis of basic treatment such as ACEI/ARB, application of YQG combined with low-dose TWT had better effect in controlling proteinuria of CPG patients, and could help stabilizing their conditions with less adverse reactions.

[Effects of Dahuang Zhechong Pill on expressions of tissue inhibitor of metalloproteinase-1 and plasminogen activator inhibitor-1 in rats with glomerulosclerosis].

OBJECTIVE: To explore the mechanisms of the beneficial effects of Dahuang Zhechong Pill (DHZCP), a Chinese patent herbal medicine, in treatment of chronic renal disease, and to investigate the effects of DHZCP on the expressions of renal tissue inhibitor of metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1) mRNAs in rats with adriamycin-induced glomerulosclerosis. METHODS: Focal segmental glomerulosclerosis and diffuse mesangial proliferation were induced in rats by combined procedures, including unilateral nephrectomy, intravenous injection of adriamycin and giving high-fat foods. The rats were randomly divided into untreated group, benazepril-treated group and DHZCP-treated group. Another 6 rats were sham-operated as control group. After 12-week treatment, rats were sacrificed, reverse transcription polymerase chain reaction (RT-PCR) method and computerized image analytical technique were used to determine the expressions of TIMP-1 and PAI-1 mRNAs. RESULTS: Compared with the untreated group, the ratios of TIMP-1/beta-actin and PAI-1/beta-actin of the DHZCP-treated group were decreased, suggesting that DHZCP could down-regulate the expressions of TIMP-1 and PAI-1 mRNAs (P<0.05). Benazepril could significantly inhibit the expression of TIMP-1 mRNA compared with that of the untreated group (P<0.05) CONCLUSION: DHZCP can down-regulate the expressions of TIMP-1 and PAI-1 mRNAs in renal tissues of rats with focal segmental glomerulosclerosis and diffuse mesangial proliferation, which may be its action mechanism in treating chronic renal disease.