Vascular and metabolic effects of metformin added to insulin therapy in patients with type 1 diabetes: A systematic review and meta-analysis.

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) is increasing among youth worldwide, translating to an increased risk ofearly-onset cardiovascular disease (CVD). Mounting studies have shown that metformin may reduce maximal carotidintima-media thickness (cIMT), improve insulin resistance and metabolic control in subjects with T1DM, and thus, may extend cardioprotective benefits. This systematic review and meta-analysis was performed to assess the efficacy and safety of metformin added to insulin therapy on reducing CVD risks and improving metabolism in T1DM. METHODS: PubMed, EMBASE, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) that compared metformin and insulin combination (duration ≥3 months) to insulin treatment alone in T1DM. Data were expressed as weighted/standardized mean differences (MDs/SMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, along with 95% confidence intervals (CIs). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to evaluate the overall certainty of the evidence. RESULTS: Nineteen RCTs (n = 1540) met the eligibility criteria. Metformin treatment significantly reduced carotid artery intima-media thickness (MD -0.06 mm [95% CI -0.88, -0.28], P < .001). Though no significant difference was found in insulin sensitivity (SMD 2.21 [95% CI -1.88, 6.29], P = .29), the total daily insulin dosage (SMD -0.81 [95% CI -1.25, -0.36], P < .001) along with traditional CVD risk factors showed improvement by better glycaemic control, partial lipid profiles, diastolic blood pressure, and limited weight gain, with neutral effect on diabetic ketoacidosis, lactic acidosis, and hypoglycaemia. However, metformin therapy increased the incidence of gastrointestinal adverse events. CONCLUSIONS: Metformin with insulin has the potential to retard the progression of atherosclerosis and provides better metabolic control in patients with T1DM, and thus, providing a potential therapeutic strategy for patients with T1DM on reducing CVD risks.

[Nitritation Performance of Zeolite Moving Bed Biofilm Reactor for Ammonium Wastewater Treatment].

A new type of zeolite-suspended packing was developed by using zeolite as an important raw material, which was then used to start the zeolite moving bed biofilm reactor (ZMBBR). ZMBBR was compared with the ceramsite moving bed biofilm reactor (CMBBR) packed with ordinary ceramsite-suspended packing to investigate the different nitritation performance. The results showed that stable nitritation was successfully achieved in two reactors by the inhibitory effect of free ammonia (FA), and both of their nitrite accumulation rates (NAR) reached 90%; due to the adsorption of zeolite to ammonium, ZMBBR relieved the inhibition of FA on AOB faster than CMBBR and achieved nitritation earlier; CMBBR and ZMBBR could maintain long-term stable nitrosation when ρ(NH4+-N) was 350 mg·L-1 and 1050 mg·L-1 and NPRAVG was 0.43 kg·(m3·d)-1 and 1.26 kg·(m3·d)-1, respectively, and ARECMBBR=82.21% and AREZMBBR=88.85%. In the process of the influent ρ(NH4+-N) gradually increasing from 250 mg·L-1 to 1250 mg·L-1, the maximum nitrite production rate (NPR) of CMBBR was 0.5634 kg·(m3·d)-1; when ρ(FA) reached 166 mg·L-1 at the influent ρ(NH4+-N) of 750 mg·L-1, CMBBR broke down for the heavy inhibition of FA. The maximum NPR of ZMBBR was 1.800 kg·(m3·d)-1, and the performance of ZMBBR was getting worse after the ρ(FNA) reached the peak value of 1.9611 mg·L-1 at the influent ρ(NH4+-N) of 1250 mg·L-1. Subsequently, the ρ(FA) of ZMBBR reached 158 mg·L-1 rapidly, the NPR dropped significantly to 0.9028 kg·(m3·d)-1, and the performance of ZMBBR became significantly worse. It was demonstrated by high-throughput sequencing analysis that the dominant strain of ZMBBR and CMBBR was Nitrosomonas_europaea, and the relative abundances of N._europaea in ZMBBR and CMBBR were 11.15% and 10.92%, respectively.

[Promoting Nitrogen Removal in ANAMMOX Biofilm Reactor by Fe2+ Under Low Nitrogen Concentration].

The feasibility for nitrogen removal in a two-stage ANAMMOX biofilm reactor promoted by Fe2+ under low nitrogen concentration was investigated. The results showed that the ANAMMOX reaction could be effectively promoted by a ρ(Fe2+) of 5, 10, and 15 mg·L-1. A ρ(Fe2+) of 10 mg·L-1 presented the highest promotion for the ANAMMOX reaction, with the highest nitrogen removal efficiency (NRE) of 81.71% under a ρ(TN) of 150 mg·L-1and a nitrogen loading rate (NLR) of 0.62 kg·(m3·d)-1. Fe2+ promoted the secretion of extracellular polymeric substance (EPS) and the synthesis of heme c in the ANAMMOX system. Batch test results further verified the positive effects by Fe2+on the activity of anaerobic ammonium oxidizing bacteria (AnAOB). The specific ANAMMOX activity (SAA) of 10 mg·L-1 ρ(Fe2+) was 3.6 times as high as that of the control group[ρ(Fe2+)=0 mg·L-1], whereas the activity of AnAOB was significantly inhibited with ρ(Fe2+) increased to 20 mg·L-1. High-throughput sequencing results showed that the addition of Fe2+ increased the abundance of Candidatus_Kuenenia. When ρ(Fe2+) was 10 mg·L-1, the relative abundance of Candidatus_Kuenenia in reactor 1 and reactor 2 increased to 16.18% and 4.22%, respectively. The stable operation of the two-stage ANAMMOX biofilm process promoted by Fe2+provides an alternative technology for low-strength nitrogen wastewater.

Effects of plant polyphenols on ovarian follicular reserve in aging rats.

The pool of ovarian primordial follicles is established during embryonic development or at birth. During the development from primordial to primary, secondary, and antral follicles, only a small portion of follicles can mature and successfully ovulate; the others are destined to degenerate through apoptotic or atretic loss. As aging advances, females ultimately enter the cessation phase of the estrous cycle and are no longer capable of fertilization. The presumption is that if we can slow down the process of folliculogenesis or decrease follicle loss, females may have a larger ovarian follicular reserve and a longer reproductive lifespan. In our study, rats underwent intragastric administration with tea polyphenols, quercetin (meletin), genistein, or resveratrol, once a day for 4 months (from age 12 to 15 months), to test whether they have positive effects on follicular reserve or ovarian functions. The results showed that rats treated with tea polyphenols (27.8 +/- 3.2) and quercetin (36.5 +/- 4.1) had a comparable number of healthy follicles to those of controls (26.9 +/- 3.8), although significantly fewer atretic follicles were observed in the tea polyphenol group (43.4 +/- 5.9 vs 79.7 +/- 7.5; p < 0.001). Remarkably, both genistein- and resveratrol-treated rats had more healthy follicles (respectively, 42.8 +/- 3.9, p < 0.05; and 51.9 +/- 6.4, p < 0.001) and fewer atretic follicles (respectively, 58.4 +/- 8.0, p < 0.05; and 51.0 +/- 6.2, p < 0.01) than controls. These results indicate that genistein and resveratrol can increase the ovarian follicular reserve and prolong the ovarian lifespan in rats, and their positive effects may be not only due to their intervention in the transition from primordial to primary follicle, but also due to the inhibiting effect on follicular atresia.

[Nitrogen Removal from Mature Landfill Leachate via Denitrification-Partial Nitritation-ANAMMOX Based on a Zeolite Biological Aerated Filter].

A combined process of denitrification-partial nitritation-ANAMMOX based on a zeolite biological aerated filter (ZBAF) was applied to treat mature landfill leachate. We investigate the partial nitritation characteristics of the ZBAF and the nitrogen removal performance as well as the carbon removal performance of the combined process. Results showed that, based on the selective inhibition of nitrite oxidizing bacteria (NOB) by free ammonia (FA), the ZBAF could successfully achieve stable and efficient partial nitrification of mature landfill leachate, with an average nitrite accumulation rate (NAR) of 93.8% and a maximum nitrite production rate (NPR) of 1.659 kg·(m3·d)-1. After adding 700 mg·L-1 glucose to the influent, due to the synergistic effect of denitrification and anammoxidation, the combined process achieved its best nitrogen removal performance at a reflux ratio of 2.0 and hydraulic retention time (HRT) of 2.2 days. The average ammonia removal efficiency (ARE), total nitrogen removal efficiency (NRE), total nitrogen removal loading rate (NRR), and average chemical oxygen demand (COD) removal efficiency were 97.2%, 90.0%, 0.585 kg·(m3·d)-1, and 45.3%, respectively. Furthermore, the NRR of the anaerobic ammonium oxidation (ANAMMOX) process (NRRANA) reached 1.268 kg·(m3·d)-1. High-throughput sequencing technology was used to analyze the microbial community structure in each device. Results showed that denitrifiers (Paracoccus and Comamonas), ammonia-oxidizing bacteria (AOB) (Nitrosomonas), and ANAMMOX bacteria (Candidatus Kuenenia and Candidatus Anammoxoglobus) were the dominant bacteria in the UASB, ZBAF, and ANAMMOX reactor, respectively, which corresponded to the stable nitrogen removal performance of the combined process.

DEPTOR expression negatively correlates with mTORC1 activity and tumor progression in colorectal cancer.

The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers, including colorectal cancer (CRC). DEPTOR is an mTOR inhibitor whose expression is negatively regulated by mTOR. However, the role of DEPTOR in the development of CRC is not known. The aim of this study was to investigate the expression of DEPTOR and mTORC1 activity (P-S6) in a subset of CRC patients and determine their relation to tumor differentiation, invasion, nodal metastasis and disease-free survival. Here, Immunohistochemical expression of P-S6 (S235/236) and DEPTOR were evaluated in 1.5 mm tumor cores from 90 CRC patients and in 90 samples of adjacent normal mucosa by tissue microarray. The expression of P-S6 (S235/236) was upregulated in CRC, with the positive rate of P-S6 (S235/236) in CRC (63.3%) significantly higher than that in control tissues (36.7%, 30%) (p<0.05). P-S6 (S235/236) also correlated with high tumor histologic grade (p=0.002), and positive nodal metastasis (p=0.002). In contrast, the expression level of DEPTOR was correlated with low tumor histological grade (p=0.006), and negative nodal metastasis (p=0.001). Interestingly, P-S6 (S235/236) expression showed a significant negative association with the expression of DEPTOR in CRC (p=0.011, R= -0.279). However, upregulation of P-S6 (S235/236) (p=0.693) and downregulation of DEPTOR (p=0.331) in CRC were not significantly associated with overall survival. Thus, we conclude that expression of DEPTOR negatively correlates with mTORC1 activity and tumor progression in CRC. DEPTOR is a potential marker for prognostic evaluation and a target for the treatment of CRC.

Effects of genistein on ovarian follicular development and ovarian life span in rats.

Recently, studies reported that neonatal genistein treatment inhibited breakdown of oocyte nests and increased oocyte survival, resulting in multi-oocyte survival in adult mice. However, whether the inhibition effect in ovarian follicular development exists also in other stages during ovarian development (e.g. adult or climacteric) is unknown. So far, few studies have investigated the effect of genistein in adult or pre-menopausal ovarian follicular development and follicular reserves. We investigated ovarian follicular development in 4-month and 15-month-old rats after 4 weeks and 4 months treatment with genistein in a dose of 160 mg/kg d. Genistein-treated rats obtained a higher percentage of primordial follicles by 4 months of age and a greater number of surviving follicles at 15 months of age compared to a control group (P<0.05). In addition, vaginal cytology showed that age-dependent cessation of regular estrus was delayed for 2 months in the genistein-treated group than control group. These results suggest that genistein alters rat ovarian follicular development and increases the number of surviving follicles, which may prolong ovarian reproductive life.