The effects of curcumin on anthropometric and cardiometabolic parameters of patients with metabolic related diseases: a systematic review and dose-effect meta-analysis of randomized controlled trials.

Objective:To perform a meta-analysis of published randomized controlled trials (RCTs) to assess the effects of curcumin supplementation with different formulations on anthropometric and cardiometabolic indices in patients with metabolism-related diseases (MRDs). Methods: Six databases, including PubMed, Embase, Web of Science, China national knowledge internet (CNKI), Wanfang and China Biology Medicine (CBM), were systematically searched to find relevant articles from 2011 to July 2021. The effect sizes were expressed as weighted mean difference (WMD) with 95% confidence intervals (CI). Between-study heterogeneity was assessed using I2. Subgroup analysis was conducted to find possible sources of heterogeneity. Curcumin formulations in this study were divided as low bioavailability, high bioavailability and nanocurcumin. Results: Of the retrieved 1585 articles, 31 were included in the final analysis. Combined effect sizes suggested a significant effect of curcumin supplementation on reduced body weight (BW) (WMD: -0.94 kg, 95% CI: -1.40, -0.47) and body mass index (BMI) (WMD: -0.40 kg/m2, 95% CI: -0.60, -0.19), respectively. The results also showed significant improvements of fasting plasma glucose (FPG) (WMD: -0.50 mg/dL, 95% CI: -0.72, -0.28), glycosylated hemoglobin (Hb1Ac) (WMD: -0.42%, 95% CI: -0.57, -0.26), insulin (INS) (WMD: -1.70 µIU/mL, 95%CI: -2.03, -1.38), homeostasis model assessment-insulin resistance (HOMA-IR) (WMD: -0.71, 95%CI: -1.11, -0.31), high-density lipoprotein cholesterol (HDL-C) (WMD: 1.73 mg/dL, 95%CI: 0.78, 2.68) and high sensitivity C-reactive protein (Hs-CRP) (WMD: -1.11, 95%CI: -2.16, -0.05). Nanocurcumin showed a greater reduction in FPG (WMD: -1.78 mg/dL, 95% CI: -2.49, -1.07), INS (WMD: -1.66 µIU/mL, 95% CI: -3.21, -0.11), TC (WMD: -12.64 mg/dL (95% CI: -23.72, -1.57) and LDL-C (WMD: -8.95 mg/dL, 95% CI: -16.51, -1.38). The dose-effect analysis showed that there were trends of first rising and then falling between the supplemented curcumin dose and BW, BMI, LDL-C, Hb1Ac, which were clearly distinguished at 80 mg/d due to the strong effect of nanocurcumin on outcomes. A slow upward trend between the dose of curcumin supplementation and HDL-C. No relationships between dose and outcomes were found for FPG and insulin, except for nanocurcumin at 80 mg/d. Conclusions: Our study showed some significant beneficial effects of curcumin supplementation on improving BW, BMI, and the levels of FPG, Hb1Ac, HOMA-IR, HDL-C and Hs-CRP in patients with MRDs. Nanocurcumin may have a greater effect on the reduction of FPG, INS, TC and LDL-C than other curcumin formulations. Considering the potential bias and limitations of studies included, further quality studies with larger sample sizes are needed to confirm these results.

Direct start-up of aerobic granular sludge system with dewatered sludge granular particles as inoculant.

Aerobic granular sludge (AGS) is a promising technology for engineering applications in the biological treatment of sewage. New objective is to skip the conventional granulation step to integrate it into a continuous-flow reactor directly. This study proposed a method for integrating spherical pelletizing granular sludge (SPGS) into a new patented aerobic granular sludge bed (AGSB), a continuous up-flow reactor. AGSB system could be startup directly, and after 120 days of operation, the SPGS maintained a relatively intact spherical structure and stability. With an initial high chemical oxygen demand (COD) volume loading of over 2.0 kg/(m3·d), this system achieved the desired effect as the same as a mature AGS system. The final mixed liquid suspended solids, and the ratio of 30 min-5 min sludge volume index (SVI30/SVI5) were 20,000 mg/L, and 0.84, respectively. Although hydraulic elution and filamentous bacteria (FBs) had a slightly negative impact on initial phase pollutant removal, the final removal rates for COD, total nitrogen (TN), ammonia nitrogen (NH4+-H), and total phosphorus (TP) were 90%, 70%, 95%, and 85%, respectively. The presence of specific functional microorganisms promoted the secretion of extracellular polymeric substances (EPS), from 90.65 to 209.78 mg/gVSS. The maturation process of SPGS altered the microbial community structures and reduced the species abundance of microbes in sludge.

Effects of Calf Blood-Deproteinized Extract Ophthalmic Gel Combined with Sodium Hyaluronate Eye Drops on Conjunctival Hyperemia Score and Tear Film Stability in Patients with Dry Eye.

Objective: The aim of this paper is to research the impact of calf blood-deproteinized extract ophthalmic gel combined with sodium hyaluronate eye drops on conjunctival hyperemia score and tear film stability in patients having dry eye. Methods: 144 patients having dry eye disease who were hospitalized from July 2018 to July 2021 were chosen as the research targets, which were composed of the control group and research group on the basis of the sequences of hospitalization, and each has 72 cases. The sodium hyaluronate eye drops were gained in the control one. In accordance with the control one, the study ones were given the combined treatment with eye drops of sodium hyaluronate. Treatment of calf blood-deproteinized extract ophthalmic gel, the scores of conjunctival hyperemia, tear film stability, visual function, curative effect, and their adverse reactions were observed and made comparisons among the two groups. Results: After the treatments of 2 weeks and later 1 month, the numerical values of the conjunctival hyperemia were fewer in the categories which had been mentioned above, and in contrast with the control one (P < 0.05), the numerical values of the conjunctival hyperemia in the study one were distinctly fewer. The data of SIt, BUT, and the heights of the central tear river of the lower eyelid were higher than those before cure. In comparison with the control one, the FL of the study one was distinctly lower, and the heights of SIt, BUT, and the central tear river of the lower eyelid were obviously better than the control one (P < 0.05). After therapy, the visual contrast sensitivity of the patients in two categories at 6.4 c/d and 12c/d increased in comparison with those before treatment, and the visual contrast sensitivity of the study group at 6.4 c/d and 12c/d was apparently higher than the data of control one (P < 0.05); the effective rate of treatment in the study one was 97.22%, which had a higher situation than the control one, 88.89% (P < 0.05); the probability of occurrence of the negative events in the study one after treatment was 4.17%, which was distinctly below the control one, 15.28% (P < 0.05). Conclusion: In order for the treatments of patients having dry eye disease, the use of calf blood-deproteinized extract ophthalmic gel having the combinations with eye drops of sodium hyaluronate can enhance the extent of visual impairment and conjunctival hyperemia with effect and improve the stability of tear film, with significant safety and high efficiency.

Salicylic acid in ginseng root alleviates skin hyperpigmentation disorders by inhibiting melanogenesis and melanosome transport.

Abnormal melanogenesis and melanosome transport can cause skin pigmentation disorders that are often treated using ginseng-based formulation. We previously found that phenolic acid compounds in ginseng root could inhibit melanin production and as a skin-whitening agents. However, mechanisms of action underlying effects of ginseng phenolic acid monomers on melanogenesis remain unclear. This study was conducted to investigate effects of salicylic acid, a main ginseng root phenolic acid component, on melanogenesis and melanosome functions in melanocytes of zebrafish and other species. Salicylic acid exhibited no cytotoxicity and reduced melanin levels and tyrosinase activity in B16F10 murine melanoma cells and normal human epidermal melanocytes regardless of prior cell stimulation with α-melanocyte stimulating hormone. Additionally, salicylic acid treatment reduced expression of melanogenic enzymes tyrosinase, tyrosinase-related protein 1 and tyrosinase-related protein 2, while reducing expression of their master transcriptional regulator, microphthalmia-associated transcription factor. Moreover, reduced phosphorylation of cAMP response-element binding protein was observed due to reduced cAMP levels resulting from salicylic acid inhibition of upstream signal regulators (adenylyl cyclase and protein kinase A). Furthermore, salicylic acid treatment suppressed expression of transport complex-associated proteins melanophilin and myosin Va in two UVB-treated melanocytic cell lines, suppressed phagocytosis of fluorescent microspheres by UVB-stimulated human keratinocytes (HaCaT), inhibited protease-activated receptor 2 activation by reducing both Ca2+ release and activation of phosphoinositide 3 kinase/AKT and mitogen-activated protein kinases and induced anti-melanogenic effects in zebrafish. Collectively, these results indicate that salicylic acid within ginseng root can inhibit melanocyte melanogenesis and melanin transport, while also suppressing keratinocyte phagocytic function.

Akt activation-dependent protective effect of wild ginseng adventitious root protein against UVA-induced NIH-3T3 cell damage.

Prolonged skin exposure to ultraviolet radiation can lead to development of several acute and chronic diseases, with UVA exposure considered a primary cause of dermal photodamage. We prepared a wild ginseng adventitious root extract (ARE) that could alleviate UVA irradiation-induced NIH-3T3 cell viability decline. After employing a series of purification methods to isolate main active components of ARE, adventitious root protein mixture (ARP) was identified then tested for protective effects against UVA irradiation-induced NIH-3T3 cell damage. The results showed that ARP treatment significantly reduced UVA-induced cell viability decline and confirmed that the active constituent of ARP was the protein, since proteolytic hydrolysis and heat treatment each eliminated ARP protective activity. Moreover, ARP treatment markedly inhibited UVA-induced apoptosis, cell cycle arrest and DNA fragmentation, while also significantly reversing UVA effects (elevated Bax levels, reduced Bcl-2 expression) by reducing Bax levels and increasing Bcl-2 expression. Mechanistically, ARP promoted Akt phosphorylation regardless of UVA exposure, thus confirming ARP resistance to inactivation by UVA light. Notably, in the presence of Akt inhibitor SC0227, ARP could no longer counteract UVA-induced cell viability decline and DNA fragmentation. Additionally, our results demonstrated that ARP treatment protected UVA-irradiated NIH-3T3 cells by preventing UVA-induced reduction of collagen-I expression. Taken together, these results suggest that ARP treatment of NIH-3T3 cells effectively mitigated UVA-induced cell viability decline by activating intracellular Akt to reduce UVA-induced DNA damage, leading to reduced rates of apoptosis and cell cycle arrest after UVA exposure and restoring collagen expression to normal levels.

Peripheral Nerve Stimulation in Pain Management: A Systematic Review.

BACKGROUND: Peripheral nerve stimulation (PNS) has been increasingly used to manage acute and chronic pain. However, the level of clinical evidence to support its use is not clear. OBJECTIVES: To assess the clinical evidence of PNS in the treatment of acute or chronic pain. STUDY DESIGN: A systematic review of the efficacy and safety of PNS in managing acute or chronic pain. METHODS: Data sources were PubMed, Cochrane Library, Scopus, CINAHL Plus, Google Scholar, and reference lists. The literature search was performed up to December 2019. Study selection included randomized trials, observational studies, and case reports of PNS in acute or chronic pain. Data extraction and methodological quality assessment were performed utilizing Cochrane review methodologic quality assessment and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR). The evidence was summarized utilizing principles of best evidence synthesis on a scale of 1 to 5. Data syntheses: 227 studies met inclusion criteria and were included in qualitative synthesis. RESULTS: Evidence synthesis based on randomized controlled trials (RCTs) and observational studies showed Level I and II evidence of PNS in chronic migraine headache; Level II evidence in cluster headache, postamputation pain, chronic pelvic pain, chronic low back and lower extremity pain; and Level IV evidence in peripheral neuropathic pain, and postsurgical pain. Peripheral field stimulation has Level II evidence in chronic low back pain, and Level IV evidence in cranial pain. LIMITATIONS: Lack of high-quality RCTs. Meta-analysis was not possible due to wide variations in experimental design, research protocol, and heterogeneity of study population. CONCLUSIONS: The findings of this systematic review suggest that PNS may be effective in managing chronic headaches, postamputation pain, chronic pelvic pain, and chronic low back and lower extremity pain, with variable levels of evidence in favor of this technique.

Protective Effects of Ginseng Proteins on Photoaging of Mouse Fibroblasts Induced by UVA.

UVA can penetrate dermis and cause functional damage of dermal fibroblasts leading photoaging. Ginseng is a widely used traditional Chinese medicine for skin aging. However, its effects on skin photoaging induced by UVA are not clear. In this study, we isolated ginseng proteins (GP), with molecular weights of 27 kDa and 13 kDa, and found that they alleviated the inhibitory effects of UVA on cell viability and increased percentage of NIH-3T3 fibroblasts in the S phase of cells cycle. GP also improved cell contraction ability, increased the expression and secretion of CoL-I, similar to MAPK phosphorylation inhibitors and reduced expression and secretion of MMP-1, MMP-2 and MMP-9 as well as the enzyme activities of MMP-2 and MMP-9. They reduced ROS content, DNA damage and 8-OHdG content, as well as the protein expression of p53, p21 and p16. The levels of p-ERK, p-p38 and p-JNK, p-c-Fos and p-c-Jun proteins were decreased by GP. Inactivated GP did not inhibit the cellular activity and expression and secretion of CoL-I irradiated by UVA. The results showed that GP can improve cell viability and contractile function by inhibiting DNA damage and collagen degradation to inhibit the photoaging effects of skin dermal cells caused by UVA.

Hawthorn Extract Alleviates Atherosclerosis through Regulating Inflammation and Apoptosis Related Factors: An Experimental Study.

OBJECTIVE: To determine the effects of hawthorn extract on serum lipid levels, pathological changes in aortic atherosclerosis plaque, inflammatory factors, and apoptosis-related protein and mRNA expression in apolipoprotein E gene knockout (ApoE-/-) mice. METHODS: Thirty-six ApoE-/- mice were fed with a high-fat diet starting at the age of 8 weeks. Mice were randomly divided into 3 groups by a random number table including model group, hawthorn extract group, and simvastatin group, 12 mice in each group. Twelve 8-week-old C57BL/6 mice were fed a basic diet and served as control. The mice in the control and model groups were administered 0.2 mL saline daily, the mice in the hawthorn extract and simvastatin groups were administered with 50 mg/kg hawthorn extract or 5 mg/kg simvastatin daily for 16 weeks. After 16 weeks, plasma lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined by an enzymatic assay. Aortic atherosclerotic lesions were observed by light microscopy, scanning and transmission electron microscopy, respectively. Plasma levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-1ß (IL-1ß), adiponectin (APN), and hypersensitive C-reactive protein (hs-CRP) were measured by enzyme-linked immunosorbent assay (ELISA). Protein and mRNA expressions of Bax and Bcl-2 in the aorta were assessed by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. RESULTS: Compared to the control group, the plasma levels of TC, TG and LDL-C were significantly increased and HDL-C were significantly decreased in the model group (P<0.01). Compared to the model group, treatment with hawthorn extract significantly decreased the plasma levels of TC, TG, and LDL-C and increased the plasma level of HDL-C in ApoE-/- mice (P<0.01). The levels of MCP-1, IL-1ß, and hs-CRP in the model group were significantly increased and APN was significantly decreased compared with the control group (P<0.01). Compared to the model group, treatment with hawthorn extract decreased the levels of MCP-1, IL-1ß, and hs-CRP and increased the APN level (P<0.01). Compared to the control group, the protein and mRNA expression of Bax in the model group were significantly increased and the expression of Bcl-2 was significantly decreased (P<0.01). Hawthorn extract also reduced the protein and mRNA expression of Bax and increased the Bcl-2 expression in the aorta (P<0.01). CONCLUSION: Hawthorn extract has anti-atherosclerosis and stabilizing unstable plaque effects. The mechanism may be related to the inflflammation and apoptosis signaling pathways.

The Effects of Environmental Factors on Ginsenoside Biosynthetic Enzyme Gene Expression and Saponin Abundance.

Panax ginseng C.A. Meyer is one of the most important medicinal plants in Northeast China, and ginsenosides are the main active ingredients found in medicinal ginseng. The biosynthesis of ginsenosides is regulated by environmental factors and the expression of key enzyme genes. Therefore, in this experiment, ginseng in the leaf opened stage, the green fruit stage, the red fruit stage, and the root growth stage was used as the test material, and nine individual ginsenosides and total saponins (the sum of the individual saponins) were detected by HPLC (High Performance Liquid Chromatography). There was a trend of synergistic increase and decrease, and saponin accumulation and transfer in different tissues. The expression of key enzyme genes in nine synthetic pathways was detected by real-time PCR, and the correlation between saponin content, gene expression, and ecological factors was analyzed. Correlation analysis showed that in root tissue, PAR (Photosynthetically Active Radiation) and soil water potential had a greater impact on ginsenoside accumulation, while in leaf tissue, temperature and relative humidity had a greater impact on ginsenoside accumulation. The results provide a theoretical basis for elucidating the relationship between ecological factors and genetic factors and their impact on the quality of medicinal materials. The results also have guiding significance for realizing the quality of medicinal materials.

Surgical treatment of medically refractory gastroparesis in the morbidly obese.

INTRODUCTION: Surgical management of medically refractory gastroparesis remains a challenge. Case series and small retrospective studies describe clinical benefits from surgical intervention; however, no study reports the efficacy of gastric electrical stimulation (GES) or Roux-en-Y gastrojejunostomy with or without near-total gastrectomy (RYGJ) in morbidly obese patients with severe gastroparesis. METHODS: A chart review was performed on all morbidly obese patients (BMI > 35 kg/m(2)) who underwent GES or RYGJ for medically refractory gastroparesis from March 2002 to December 2012 at the Cleveland Clinic. The main outcomes examined were symptom improvement, postoperative complications, and change in BMI. RESULTS: A total of 20 morbidly obese patients underwent GES placement. Seven morbidly obese patients had RYGJ with or without resection of the remnant stomach surgery. All operations were completed laparoscopically. In GES group, 18 patients had initial symptom improvement (90%) and 11 (55%) rated their symptom improved at the last follow-up. During the average 23 months' follow-up, 9 patients (45%) experienced at least one readmission for gastrointestinal reasons. Early complications included two infections at a simultaneously placed J-tube site and one seroma. In the RYGJ group, all patients, including 4 patients who failed GES and subsequently converted to RYGJ, experienced short-term symptom improvement and 5 patients (71%) rated their symptoms as improved at last follow-up. One duodenal stump leak happened in the RYGJ group. There were no 30-day mortalities in either group. The BMI change after GES implantation was 0.6 ± 4 kg/m(2) versus -7.7 ± 4 kg/m(2) after RYGJ (p < 0.01). CONCLUSION: GES implantation and RYGJ are both effective in terms of symptom control for medically refractory gastroparesis in morbidly obese. Both options can be performed in a minimally invasive fashion with low morbidity. Patients who have no improvement of symptoms for refractory gastroparesis after GES implantation can be successfully converted laparoscopically to RYGJ.