Network meta-analysis of curative efficacy of different acupuncture methods on obesity combined with insulin resistance.

Objective: This study aims to systematically evaluate the curative efficacy of different acupuncture methods in the treatment of obesity combined with insulin resistance in randomized clinical trials (RCTs) by network meta-analysis. Methods: Four Chinese databases (CNKI, WanFang Data, VIP, and SinoMed) and four English databases (PubMed, Embase, the Cochrane Library, and www.clinicaltrial.gov) were electronically searched to identify qualified studies. Two reviewers independently screened the literature in accordance with the inclusion/exclusion criteria by EndNote 20 software and extracted data by ADDIS1.16.8 software, and then the risk of bias of the included studies were evaluated by the Cochrane tool. Network meta-analysis was performed by Stata 15.1 software. The primary outcomes included fasting blood glucose (FBG), fasting serum insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR), and body mass index (BMI). The secondary outcomes included waistline, waist-hip ratio, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Results: Five RCTs with a total of 410 patients with obesity combined with insulin resistance were included. The results of the network meta-analysis showed that, compared with the control group, three kinds of acupuncture methods (electropuncture, acupoint catgut embedding, and acupuncture point patch) had significant efficacy in reducing FBG [electropuncture (MD = -0.44, 95% CI: -0.83, -0.05) and acupoint catgut embedding (MD = -0.36, 95% CI: -0.51, -0.21)], FINS [electropuncture (MD = -6.17, 95% CI: -9.69, -2.65), acupoint catgut embedding (MD = -5.87, 95% CI: -6.92, -4.82), and acupuncture point patch (MD = -5.86, 95% CI: -11.40, -0.32)], HOMA-IR [electropuncture (MD = -1.59, 95% CI: -2.73, -0.45) and acupoint catgut embedding (MD =-0.91, 95% CI: -1.07, -0.75)], BMI [electropuncture (MD = -1.68, 95% CI: -2.70, -0.66), acupoint catgut embedding (MD = -3.39, 95% CI: -4.38, -2.40), and acupuncture point patch [MD = -2.90, 95%CI: -4.93, -0.87)], and waistline [electropuncture (MD = -5.49, 95% CI: -8.56, -2.42) and acupoint catgut embedding (MD = -4.91, 95% CI: -7.51, -2.31)] in obese patients with insulin resistance, suggesting that their efficacy was better than that of the western medicine group in some of the outcome indicators. For the index related to blood lipid, the efficacy of electropuncture was significantly better than behavioral therapy and western medicine. Except that acupoint catgut embedding was superior to electroacupuncture in reducing the BMI, there was no statistically significant difference in efficacy among the three acupuncture methods. Conclusions: The results showed that the therapeutic effect of acupuncture methods was superior to conventional western treatment alone. Acupuncture methods could serve as an alternative or adjunctive treatment in obese patients with insulin resistance. Systematic Review Registration: https://inplasy.com, identifier 202280075.

Lipid metabolism disorders contribute to hepatotoxicity of ICR mice induced by nitrosamines exposure.

Health risks caused by crucial environmental carcinogens N-nitrosamines triggered ubiquitous attention. As the liver exerted vital function through metabolic process, lipid metabolism disorders have been confirmed as potential drivers for toxicological effects, and the mechanisms of lipid regulation related to hepatotoxicity induced by N-nitrosamines remained largely unclear. In this study, we comprehensively explored the disturbance of hepatic lipid homeostasis in mice induced by nitrosamines. The results implied that nitrosamines exposure induced hepatotoxicity accompanied by liver injury, inflammatory infiltration, and hepatic edema. Lipidomics profiling analysis indicated the decreased levels of phosphatidic acids (PA), phosphatidylcholines (PC), phosphatidylethanolamines (PE), lyso-phosphatidylcholines (LPC), lyso-phosphatidylethanolamines (LPE), diacylglycerols (DAG) and triacylglycerols (TAG), the elevation of ceramides (Cer) and decomposition of free fatty acids (FFA) in high-dose nitrosamines exposure group. Importantly, nitrosamines exposure promoted fatty acid oxidation (FAO) by facilitating fatty acid uptake and decomposition, together with the upregulation of genes associated with FAO accompanied by the activation of inflammatory cytokines TNF-α, IL-1ß and NLRP3. Furthermore, fatty acid translocase CD36-mediated fatty acid oxidation was correlated with the enhancement of oxidative stress in the liver caused by nitrosamines exposure. Overall, our results contributed to the new strategies to interpret the early toxic effects of nitrosamines exposure.

Glutathione Induced Transformation of Partially Hollow Gold-Silver Nanocages for Cancer Diagnosis and Photothermal Therapy.

Gold-silver nanocages (GSNCs) are widely used in cancer imaging and therapy due to excellent biocompatibility, internal hollow structures, and tunable optical properties. However, their possible responses toward the tumor microenvironment are still not well understood. In this study, it is demonstrated that a kind of relatively small sized (35 nm) and partially hollow GSNCs (absorbance centered at 532 nm) can enhance the intrinsic photoacoustic imaging performances for blood vessels around tumor sites. More importantly, the high concentration of glutathione around the tumor cells' microenvironment may induce the aggregation, disintegration, and agglomeration of these GSNCs sequentially, allowing significant shifts in the absorbance spectrum of GSNCs to the near-infrared (NIR) region. This enhanced absorbance in the NIR region entails the significant photothermal therapy (PTT) effect. In vivo experiments, including photoacoustic microscopy (PAM) for cancer diagnosis and PTT in tumor model mice, also show coincident consequences. Taken together, the slightly hollow GSNCs may assist PAM-based tumor diagnosis and induce a tumor targeted PTT effect. This work paves a new avenue for the development of an alternative tumor diagnostic and therapeutic strategy.

Transcriptomic-metabolomic reprogramming in EGFR-mutant NSCLC early adaptive drug escape linking TGFß2-bioenergetics-mitochondrial priming.

The impact of EGFR-mutant NSCLC precision therapy is limited by acquired resistance despite initial excellent response. Classic studies of EGFR-mutant clinical resistance to precision therapy were based on tumor rebiopsies late during clinical tumor progression on therapy. Here, we characterized a novel non-mutational early adaptive drug-escape in EGFR-mutant lung tumor cells only days after therapy initiation, that is MET-independent. The drug-escape cell states were analyzed by integrated transcriptomic and metabolomics profiling uncovering a central role for autocrine TGFß2 in mediating cellular plasticity through profound cellular adaptive Omics reprogramming, with common mechanistic link to prosurvival mitochondrial priming. Cells undergoing early adaptive drug escape are in proliferative-metabolic quiescent, with enhanced EMT-ness and stem cell signaling, exhibiting global bioenergetics suppression including reverse Warburg, and are susceptible to glutamine deprivation and TGFß2 inhibition. Our study further supports a preemptive therapeutic targeting of bioenergetics and mitochondrial priming to impact early drug-escape emergence using EGFR precision inhibitor combined with broad BH3-mimetic to interrupt BCL-2/BCL-xL together, but not BCL-2 alone.

Fabrication of CdTe@SiO2 nanoprobes for sensitive electrogenerated chemiluminescence detection of DNA damage.

Detection of DNA damage is significant for the evaluation of genotoxicity of new chemicals in the early stages of its development. An electrogenerated chemiluminescence (ECL) biosensor was fabricated to detect specific sequences of DNA by using CdTe@SiO2 as nanoprobes for signal amplification. This DNA biosensor was constructed by self-assembly of an aminated capture DNA on the glass carbon electrode. DNA detection was realized by outputting a remarkable ECL signal of the CdTe@SiO2 labeled probe DNA. When the target DNA was introduced into the system, it was complementary to the probe DNA at the one-half-segment and complementary to the capture DNA at the other half-segment, resulting in the formation of a stable duplex complex. As a result, the CdTe@SiO2 labeled probe was proximate to the electrode surface and the ECL was observed. This DNA biosensor was proved to have a low detection limit (0.03 nM) and a wide dynamic range (from 0.1 nM to 2 µM). Most importantly, the sensing system could differentiate the single base mismatched DNA from the complementary DNA. It was successfully applied to study the damage to DNA caused by several genotoxicity chemicals, which was rapid, simple, reliable and sensitive compared to the classical biological methods.

The profile of ß-amyloid precursor protein expression of rats induced by aluminum.

The environmental agent aluminum has been extensively investigated for a potential relationship with amyloid precursor protein (APP) expression. Despite many investigations, there is at present no definite proof from which to draw a conclusion. Since APP is an integral membrane protein expressed in different tissues and capable of fluxes across the blood-brain barrier (BBB), which may ultimately affect APP level in brain, it is necessary to assess the expression profile among vital body organs. The present study compared aluminum oxide and aluminum chloride injected rats with control rats (saline treated) to observe if aluminum affected APP expression patterns in different organs by immunohistochemistry (IHC). The expression of APP was observed in the brain of aluminum chloride treated rats and in the liver of aluminum oxide injected group. Results of double IHC staining showed that it is Kupffer cells, which are located in liver sinus and expressed APP after aluminum oxide treatment. Oxidative stress is suggested as the potential pathway that aluminum chloride exert effects in brain. These results suggest that different aluminum compounds may impact the expression of APP in brain and liver tissues. The mechanism that aluminum induced liver APP expression still needs further investigation.

Effects of subchronic exposure to multi-walled carbon nanotubes on mice.

Carbon nanotubes have attracted attention not only due to electrical, optical, and mechanical applications but also due to their presence in biological and pharmaceutical products. In this study, modified multi-walled carbon nanotubes (MWCNT) were used as a model to evaluate potential subchronic effects of carbon nanotubes on mice. ICR mice were treated with phosphorylcholine-grafted multi-walled carbon nanotubes (MWCNT-PC) daily for 28 d at 10, 50, or 250 mg/kg by the intraperitoneal (ip) route. Subchronic exposure to MWCNT-PC did not produce any apparent systemic effects in mice. The body weight of the high-dose group was significantly lower than control in male mice, whereas tissue to body weight ratios of liver, spleen, and lung rose significantly with increase of dose of MWCNT-PC. There were significant differences between high-dose exposure and control groups. Accumulation of carbon nanotubes and inflammation response in liver, spleen, and lung were observed in the high-dose exposure group. No systemic toxicity and histopathological changes were found in 10-mg/kg exposure groups. Data in the present study support the view that MWCNT in vivo do not exert apparent marked effects in mice and that MWCNT products are relatively safe for human consumption.

Influence of different sizes of titanium dioxide nanoparticles on hepatic and renal functions in rats with correlation to oxidative stress.

As titanium dioxide (TiO(2)) nanoparticles are widely used commercially, the potential effects of TiO(2) nanoparticles on humans are a concern. To evaluate the effects of TiO(2) nanoparticles on hepatic and renal functions and correlate changes to oxidative stress, Sprague-Dawley rats were treated with TiO(2) particles of two different specific surface areas (TiO(2-S50): 50 m(2)/g, and TiO(2-S210): 210 m(2)/g) at 0.5, 5, or 50 mg/kg body weight by intratracheal instillation. After 7 d, TiO(2) nanoparticles produced no obvious acute toxicity on hepatic and renal functions. However, superoxide dismutase (SOD) activity of plasma and glutathione peroxidase (GSH-PX) activity of kidney in the low-dose TiO(2-S210) group were significantly decreased. After TiO(2-S210) exposure, malondialdehyde (MDA) levels of liver and kidney in intermediate and high-dose groups were significantly increased. This change only appeared in liver after TiO(2-S50) exposure. Furthermore, SOD activity in liver and kidney and GSH-PX activity in kidney with low TiO(2-S210) exposure group were significantly less than with low TiO(2-S50). No apparent pathological changes in liver and kidney were observed. Intratracheal exposure to TiO(2) nanoparticles may induce oxidative stress in liver and kidney, but does not influence hepatic or renal functions. There was no apparent evidence that TiO(2-S210) was more toxic than TiO(2-S50). In general, intratracheal exposure to TiO(2) did not markedly affect extrapulmonary tissue functions.

[Interaction of beta-carotene on lipid peroxidation induced by cigarette smoke].

OBJECTIVE: To study the interaction of beta-carotene on lipid peroxidation induced by the smoke of cigarette. METHODS: Rat type II pneumocytes were isolated, cultured and then exposed to particles extracted from cigarette smoke and/or beta-carotene for 24 h. Malondialdehyde (MDA) in the cells was measured by TBA method. On the other hand, serum MDA of mice given beta-carotene supplements and/or exposed to cigarette smoke for 10 days was measured. RESULTS: The particles extracted from cigarette smoke increased the content of MDA in the rate type II pneumocytes, and the lipid peroxidation was antagonized by adding 0.5 microgram/ml of beta-carotene to the cells simultaneously. The results from the in vivo study showed that serum MDA levels were increased in the cigarette smoke-treated groups, and the lipid peroxidation was reduced by treating mice with 2.5 mg per kg body weight of beta-carotene. CONCLUSION: beta-carotene had an antagonistic effect on lipid peroxidation induced by cigarette smoke. The effective dosage of beta-carotene was 0.5 microgram/ml for rat pneumocytes and 2.5 mg/kg BW weight for mice.

[Oxidative stress of cooking oil fume on rat type II lung cells].

The relationship between the oxidative stress and damages in rat type II lung cells exposed to cooking oil fume (COF) was studied. The cytotoxicity, DNA cross-links and DNA single strand breaks could be observed in the cells exposed to COF. The contents of MDA were increased and GSH were decreased significantly with exposure doses of COF and with time dependence. Pretreatment with antioxidant N-acetylcysteine (NAC) could reduce the toxicity of COF to the cells. The results suggested that cytotoxicity and DNA damages of rat type II lung cells induced by cooking oil fume might be related to the oxidative stress and the possible pathways might be the formation of lipid peroxides and interfering the GSH anti-oxidative systems of the cells.