The effects of nutritional supplementation on older sarcopenic individuals who engage in resistance training: a meta-analysis.

Objective: Sarcopenia is a typical age-related disorder characterized by loss of muscle mass, strength, and physical function. Resistance training has a noticeable effect on sarcopenia, but there is no consensus on whether nutritional supplements can boost this effect. We conducted a meta-analysis of relevant literature to investigate the therapeutic effect of resistance training combined with nutrition intervention on sarcopenia compared with resistance training alone. Methods: Cochrane Library, PubMed, Web of Science, Embase, Sinomed, CNKI, VIP, and Wanfang Data were searched for relevant studies on resistance training combined with nutritional intervention for aging adults with sarcopenia. The retrieval period ranged from the inception of the databases to May 24, 2022. Literature screening and information extraction were performed by two researchers. The Physiotherapy Evidence Database (PEDro) scale was adopted for literature quality evaluation and Stata 15.0 software for analysis. Results: Twelve clinical trials were included, involving 713 older adults diagnosed with sarcopenia, of whom 361 were assigned to the experimental group and 352 to the control group. Compared with the control group, grip strength of the experimental group was substantially elevated [WMD = 1.87, 95% CI (0.01, 3.74), P = 0.049]. Subgroup analysis demonstrated that vitamin D and protein increased grip strength and gait speed. There were no significant improvement in grip strength and gait speed in the protein and vitamin D free subgroup. Conclusions: This meta-analysis demonstrated that resistance training combined with additional nutritional supplementation, especially compound nutritional supplements that included protein and vitamin D, might further enhance grip strength rather than muscle mass in older adults with sarcopenia. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022346734.

Observation of complications assessed by Clavien-Dindo classification in different endoscopic procedures of benign prostatic hyperplasia: An observational study.

The Clavien-Dindo classification (CDC) was widely used in the assessment of surgical complications, but some inconsistencies always existed in urological literature. This study was aimed to report complications of the transurethral resection of the prostate (TURP), plasmakinetic resection of the prostate (PKRP), and holmium laser enucleation of the prostate (HoLEP) by using a more detailed way under the framework of CDC. A total of 623 eligible cases underwent endoscopic procedures from January 2018 and December 2020 were divided into the TURP group (212 cases), the PKRP group (208 cases), and the HoLEP group (203 cases) according to the surgical type. Patients' surgical complications assessed by the CDC were compared among the 3 groups. The operation time, intraoperative irrigation volume, postoperative irrigation time and volume, decrease in hemoglobin and sodium, postoperative catheterization time, visual analogue scale, hospital stay of the PKEP group and the HoLEP group were significantly less than those of the TURP group, and the decrease in hemoglobin and visual analogue scale in the HoLEP group were significantly lower than those in the PKEP group (all P < .05). The electrolyte disturbance, urinary tract irritation, and patients with grade II of CDC in the PKRP group were significantly lower than those in the TURP group; The electrolyte disturbance, lower abdominal pain, urinary tract irritation, intraoperative hemorrhage, secondary hemorrhage, clot retention, patients with grade I, II, III of CDC in the HoLEP group were significantly lower than those in the TURP group, and the urinary tract irritation, grade I, II of CDC in the HoLEP group was significantly lower than that in the PKRP group (all P < .05). The CDC should be recommended because of the enhanced insight into surgical complications, and the HoLEP should be given a priority for Benign prostatic hyperplasia (BPH) surgical treatment in terms of the merits in surgical characteristics and complications.

Salidroside Induces Apoptosis in Human Gastric Cancer Cells via the Downregulation of ENO1/PKM2/GLUT1 Expression.

Salidroside is reported to have a wide range of pharmacological properties and has been proven to play a key anti-cancer effect. This study investigated the effects of purified salidroside, an ingredient of Rhodiola rosea, on the proliferation of two human gastric cancer cell lines and further investigating its possible molecular mechanisms. We verified that salidroside exerts a dose-dependent inhibitory effect on the proliferation of SGC-7901 and MKN-45 human gastric cancer cells. Moreover, salidroside can induce cell apoptosis, which was accompanied by an increase in nuclear fragmentation. In addition, salidroside inhibited glycolysis, as evidenced by the reduced expression levels of the glycolysis-related enzymes pyruvate kinase isoenzyme M2 (PKM2), enolase 1 (ENO1) and glucose transporter 1 (GLUT1), which could play important roles in the metabolism of gastric cancer cells. Further investigation showed that salidroside exerted potent anti-proliferative effects by inhibiting glycolysis in human gastric cancer cells in vitro. In vivo, xenograft tumors treated with salidroside were significantly smaller than those in the control animals. Therefore, salidroside could be a promising therapeutic prospect in the treatment of gastric cancer.

Dietary Betaine Mitigates Hepatic Steatosis and Inflammation Induced by a High-Fat-Diet by Modulating the Sirt1/Srebp-1/Pparɑ Pathway in Juvenile Black Seabream (Acanthopagrus schlegelii).

The present study aimed to elucidate the mechanism of dietary betaine, as a lipid-lowering substance, on the regulation of lipid metabolism and inflammation in juvenile black seabream (Acanthopagrus schlegelii) fed a high fat diet. An 8-week feeding trial was conducted in black seabream with an initial weight of 8.39 ± 0.01g fed four isonitrogenous diets including Control, medium-fat diet (11%); HFD, high-fat diet (17%); and HFD supplemented with two levels (10 and 20 g/kg) of betaine, HFD+B1 and HFD+B2, respectively. SGR and FE in fish fed HFD+B2 were significantly higher than in fish fed HFD. Liver histology revealed that vacuolar fat droplets were smaller and fewer in bream fed HFD supplemented with betaine compared to fish fed HFD. Betaine promoted the mRNA and protein expression levels of silent information regulator 1 (Sirt1), up-regulated mRNA expression and protein content of lipid peroxisome proliferator-activated receptor alpha (pparα), and down-regulated mRNA expression and protein content of sterol regulatory element-binding protein-1(srebp-1). Furthermore, the mRNA expression levels of anti-inflammatory cytokines in liver and intestine were up-regulated, while nuclear factor kB (nf-kb) and pro-inflammatory cytokines were down-regulated by dietary betaine supplementation. Likewise, in fish that received lipopolysaccharide (LPS) to stimulate inflammatory responses, the expression levels of mRNAs of anti-inflammatory cytokines in liver, intestine and kidney were up-regulated in fish fed HFD supplemented with betaine compared with fish fed HFD, while nf-kb and pro-inflammatory cytokines were down-regulated. This is the first report to suggest that dietary betaine could be an effective feed additive to alleviate hepatic steatosis and attenuate inflammatory responses in black seabream fed a high fat diet by modulating the Sirt1/Srebp-1/Pparɑ pathway.

Hong-Hui-Xiang Alleviates Pain Hypersensitivity in a Mouse Model of Monoarthritis.

Background: Hong-Hui-Xiang (HHX) is a sterilized aqueous solution extracted from Illicium lanceolatum A.C. Smith widely used for pain relief in China. Despite its history, it is not well understood. In the present study, we used a mouse model of arthritic knee pain to investigate the antinociceptive effects of HHX and its potential side effects on weight and respiratory function, as well as on the liver, kidney, and heart. Methods: Mice were randomly assigned to four groups: saline and HHX at three doses (1 µl, 10 µl, and 50 µl). Each group was randomly divided to two subgroups: saline and CFA. After the first injection of HHX or saline on day 7, mechanical hyperalgesia was tested via the hind paw. Only after the tests had established that the analgesic effect had subsided was the next injection administered. A total of five injections were administered. Blood, knee joints, and other organs were collected for histopathological observation and biochemical detection. Objectives: We found that mechanical threshold of hind paw increased 2 h after of the initial injection HHX (10 µl and 50 µl), which lasted for at least 3 h. The analgesic effect lasted for three days after the second injection on day 8 and was approximately maintained for five days each time after the third injection. We also found a reduction in the diameter of the knee joint and suppression of synovial inflammation in response to treatment of HHX (10 µl and 50 µl). Meanwhile, HHX had no toxic effects on the liver, kidneys, and heart via histological and biochemical assays in all groups. Conclusion: HHX exerts antinociceptive and anti-inflammatory effects in a mouse model of arthritic knee pain. There were no obvious side effects on the liver, kidneys, or heart.

Acupuncture protects against cerebral ischemia-reperfusion injury via suppressing endoplasmic reticulum stress-mediated autophagy and apoptosis.

BACKGROUND: Acupuncture treatment possesses the neuroprotection potential to attenuate cerebral ischemia-reperfusion (I/R) injury. Endoplasmic reticulum (ER) stress has been suggested to be involved in the pathogenic mechanism of cerebral I/R injury. Whether acupuncture protects against cerebral I/R injury via regulating ER stress remains unclear. This study aimed to evaluate the role of ER stress in the neuroprotection of acupuncture against cerebral I/R injury and its underlying mechanisms. METHODS: Cerebral I/R injury was induced by middle cerebral artery occlusion (MCAO) in rats. Acupuncture was carried out at Baihui (GV 20), and Qubin (GB7) acupoints in rats immediately after reperfusion. The infarct volumes, neurological score, ER stress, autophagy and apoptosis were determined. RESULTS: Acupuncture treatment decreased infarct volume, neurological score and suppressed ER stress via inactivation of ATF-6, PERK, and IRE1 pathways in MCAO rats. Attributing to ER stress suppression, 4-PBA (ER stress inhibitor) promoted the beneficial effect of acupuncture against cerebral I/R injury. Whereas, ER stress activator tunicamycin significantly counteracted the neuroprotective effects of acupuncture. In addition, acupuncture restrained autophagy via regulating ER stress in MCAO rats. Finally, ER stress took part in the neuroprotective effect of acupuncture against apoptosis in cerebral I/R injury. CONCLUSIONS: Our findings suggest that acupuncture offers neuroprotection against cerebral I/R injury, which is attributed to repressing ER stress-mediated autophagy and apoptosis.

Senna alexandrina extract supplementation reverses hepatic oxidative, inflammatory, and apoptotic effects of cadmium chloride administration in rats.

Senna alexandrina is traditionally used for its antioxidant and anti-inflammatory properties, but little information is available concerning its potential protective effects against cadmium, which is a widespread environmental toxicant that causes hepatotoxicity. Here, we explored the effects of S. alexandrina extract (SAE) on cadmium chloride (CdCl2)-induced liver toxicity over 4 weeks in rats. Rats were allocated into four groups: control, SAE (100 mg/kg), CdCl2 (0.6 mg/kg), and SAE + CdCl2, respectively. Cadmium level in hepatic tissue, blood transaminases, and total bilirubin as indicators of liver function were assessed. Oxidative stress indices [malondialdehyde (MDA), nitrate/nitrite (NO), and glutathione (GSH)], antioxidant molecules [superoxide dismutase (SOD, catalase (CAT), glutathione-derived enzymes, and nuclear factor erythroid 2-related factor 2 (Nrf2)], pro-inflammatory mediators [interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α)], apoptosis proteins (Bcl-2, Bax, and caspase-3), and histological alterations to the liver were examined. SAE administration before CdCl2 exposure decreased cadmium deposition in liver tissue and the blood liver function indicators. SAE pre-treatment prevented oxidative, inflammatory, and apoptotic reactions and decreased histological alterations to the liver caused by CdCl2 exposure. SAE can be used as a promising protective agent against CdCl2-induced hepatotoxicity by increasing Nrf2 expression. Graphical abstract.

[Effect of traditional Chinese medicine syndrome differentiation and standard bundle therapy in patients with septic shock].

OBJECTIVE: To evaluate an effective and feasible quantitative evaluation table of traditional Chinese medicine (TCM) syndrome differentiation, and to observe the effect of combination of TCM syndrome differentiation and standard bundle therapy in patients with septic shock. METHODS: A prospective randomized controlled trial was conducted. The septic shock patients with acute deficiency syndrome admitted to department of critical care medicine of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 1st, 2016 to December 31st, 2017 were enrolled. The patients were randomly divided into control group and Shenfu group. The patients in both groups received early application of standardized bundle therapy; those in Shenfu group received 60 mL Shenfu injection infusion in addition for 7 days. The TCM syndrome score was evaluated by classification and scoring method of TCM symptoms. The circulation and tissue perfusion, severity of disease, organ function, inflammation response, adjuvant treatment and 28-day mortality were compared between the two groups. RESULTS: A total of 50 patients with septic shock were enrolled in the analysis, 25 in control group and 25 in Shenfu group. The markedly effective rate of TCM symptoms score in Shenfu group was significantly higher than that in control group [60.0% (15/25) vs. 16.0% (4/25), P < 0.01]. There was no significant difference in all parameters before treatment between the two groups. After treatment, the observation indexes of both groups were improved. Compared with control group, the mean arterial pressure (MAP) in Shenfu group increased more significantly [mmHg (1 mmHg = 0.133 kPa): 13.0 (2.5, 28.5) vs. 6.0 (0, 13.5)], the lactate (Lac) and procalcitonin (PCT) decreased more significantly [Lac (mmol/L): 0.8 (0.1, 3.7) vs. 0.5 (-0.6, 1.7), PCT (µg/L): 2.0 (0.7, 32.3) vs. 0 (-1.8, 3.8)], activated partial thromboplastin time (APTT) was shortened more significantly [s: 8.5 (0, 12.9) vs. 0 (-7.2, 10.0)], and interleukins (IL-2 receptor and IL-6) levels decreased more significantly [IL-2 receptor (ng/L): 1 031.0 (533.0, 1 840.0) vs. 525.5 (186.0, 1 166.8), IL-6 (ng/L): 153.1 (21.4, 406.8) vs. 35.1 (16.3, 110.1)] with significant differences (all P < 0.05). There was no significant difference in the use time of vasoactive drugs, duration of mechanical ventilation, severity of the disease or 28-day mortality between the two groups. However, the use time of vasoactive drugs in Shenfu group was shorter than that in control group (days: 5.48±4.81 vs. 8.28±7.83), and the 28-day mortality was decreased [8.0% (2/25) vs. 20.0% (5/25)]. CONCLUSIONS: TCM syndrome score is helpful to evaluate the effect of TCM syndrome differentiation and treatment, and it is effective and feasible in clinical application. Septic shock patients treated with TCM syndrome differentiation and treatment combined with standard bundle therapy were significantly improved in circulation, tissue perfusion, coagulation function and inflammation reaction.

PGE2 signaling via the neuronal EP2 receptor increases injury in a model of cerebral ischemia.

The inflammatory prostaglandin E2 (PGE2) EP2 receptor is a master suppressor of beneficial microglial function, and myeloid EP2 signaling ablation reduces pathology in models of inflammatory neurodegeneration. Here, we investigated the role of PGE2 EP2 signaling in a model of stroke in which the initial cerebral ischemic event is followed by an extended poststroke inflammatory response. Myeloid lineage cell-specific EP2 knockdown in Cd11bCre;EP2lox/lox mice attenuated brain infiltration of Cd11b+CD45hi macrophages and CD45+Ly6Ghi neutrophils, indicating that inflammatory EP2 signaling participates in the poststroke immune response. Inducible global deletion of the EP2 receptor in adult ROSA26-CreERT2 (ROSACreER);EP2lox/lox mice also reduced brain myeloid cell trafficking but additionally reduced stroke severity, suggesting that nonimmune EP2 receptor-expressing cell types contribute to cerebral injury. EP2 receptor expression was highly induced in neurons in the ischemic hemisphere, and postnatal deletion of the neuronal EP2 receptor in Thy1Cre;EP2lox/lox mice reduced cerebral ischemic injury. These findings diverge from previous studies of congenitally null EP2 receptor mice where a global deletion increases cerebral ischemic injury. Moreover, ROSACreER;EP2lox/lox mice, unlike EP2-/- mice, exhibited normal learning and memory, suggesting a confounding effect from congenital EP2 receptor deletion. Taken together with a precedent that inhibition of EP2 signaling is protective in inflammatory neurodegeneration, these data lend support to translational approaches targeting the EP2 receptor to reduce inflammation and neuronal injury that occur after stroke.

Dietary choline supplementation attenuated high-fat diet-induced inflammation through regulation of lipid metabolism and suppression of NFκB activation in juvenile black seabream (Acanthopagrus schlegelii).

The present study aimed to investigate whether dietary choline can regulate lipid metabolism and suppress NFκB activation and, consequently, attenuate inflammation induced by a high-fat diet in black sea bream (Acanthopagrus schlegelii). An 8-week feeding trial was conducted on fish with an initial weight of 8·16 ± 0·01 g. Five diets were formulated: control, low-fat diet (11 %); HFD, high-fat diet (17 %); and HFD supplemented with graded levels of choline (3, 6 or 12 g/kg) termed HFD + C1, HFD + C2 and HFD + C3, respectively. Dietary choline decreased lipid content in whole body and tissues. Highest TAG and cholesterol concentrations in serum and liver were recorded in fish fed the HFD. Similarly, compared with fish fed the HFD, dietary choline reduced vacuolar fat drops and ameliorated HFD-induced pathological changes in liver. Expression of genes of lipolysis pathways were up-regulated, and genes of lipogenesis down-regulated, by dietary choline compared with fish fed the HFD. Expression of nfκb and pro-inflammatory cytokines in liver and intestine was suppressed by choline supplementation, whereas expression of anti-inflammatory cytokines was promoted in fish fed choline-supplemented diets. In fish that received lipopolysaccharide to stimulate inflammatory responses, the expression of nfκb and pro-inflammatory cytokines in liver, intestine and kidney were all down-regulated by dietary choline compared with the HFD. Overall, the present study indicated that dietary choline had a lipid-lowering effect, which could protect the liver by regulating intrahepatic lipid metabolism, reducing lipid droplet accumulation and suppressing NFκB activation, consequently attenuating HFD-induced inflammation in A. schlegelii.

Efficacy and safety of recombinant human parathyroid hormone (1-34) are similar to those of alendronate in the treatment of postmenopausal osteoporosis.

The study evaluates efficacy and safety of recombinant human parathyroid hormone (1-34) [rhPTH (1-34)] and alendronate (ALN) in the treatment of postmenopausal osteoporosis.Totally 65 postmenopausal women with osteoporosis were divided into 2 groups. PTH group received daily subcutaneous injection of rhPTH (1-34), and ALN group were treated orally with ALN per week. Bone mineral density (BMD) of lumbar spine (1-4), femoral neck, and total hip, serum levels of calcium, phosphorus, total cholesterol, triglyceride, alkaline phosphatase (ALP), N-terminal propeptide of type I collagen (PINP), and C-telopeptide of type I collagen (CTX) were tested before treatment and at week 24 and 48 after treatment. Serum levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-BB (PDGF-BB) were measured before treatment and at week 48 after treatment.The rhPTH (1-34) increased BMD of lumbar spine (1-4), but decreased BMD of femoral neck and total hip at week 48 after treatment. By contrast, ALN enhanced BMD of lumbar spine (1-4) and femoral neck, but reduced BMD of total hip at week 48 after treatment. In PTH group, serum levels of PINP, ALP, and ß-CTX were significantly elevated above baseline at week 24 and 48 after treatment. Treatment with ALN decreased levels of PINP, ALP, and ß-CTX compared with baseline at week 24 and 48 after treatment. rhPTH (1-34) and ALN significantly decreased levels of PDGF-BB, but not levels of VEGF. rhPTH (1-34) increased levels of calcium, phosphorus and triglyceride, but decreased levels of total cholesterol. ALN increased levels of calcium and triglyceride, but reduced levels of phosphorus and total cholesterol. rhPTH (1-34) and ALN were safe in the treatment of postmenopausal osteoporosis.The study demonstrates that efficacy of rhPTH (1-34) on BMD of lumbar spine (1-4) is similar to that of alendronate in the treatment of postmenopausal osteoporosis. The effect of rhPTH (1-34) on BMD of femoral neck or total hip is weaker than that of ALN. In addition, rhPTH (1-34) increases BMD of lumbar spine (1-4) maybe by raising serum levels of VEGF, but reduces BMD of femoral neck and total hip maybe by decreasing serum levels of PDGF-BB.

The design, synthesis and evaluation of selenium-containing 4-anilinoquinazoline hybrids as anticancer agents and a study of their mechanism.

Inhibition of tubulin polymerization is one of the significant strategies in the treatment of cancer. Inspired by the excellent antitumor activity of EP128495 and the beneficial biological activities of selenium compounds, a series of new selenium-containing 4-anilinoquinazoline hybrids were synthesized and evaluated as tubulin polymerization inhibitors. An anti-proliferative activity assay showed that most of the compounds inhibited human sensitive cancer cells at low nanomolar concentrations. A mechanism study revealed that the optimal compound 5a disrupted microtubule dynamics, decreased the mitochondrial membrane potential and arrested HeLa cells in the G2/M phase, finally resulting in cellular apoptosis.