PKM2 is a Novel Osteoporosis-Associated Protein in Chinese.

Purpose:Osteoporosis is characterized by low bone mineral density (BMD) and high risk of osteoporotic fracture (OF). Peripheral blood monocytes (PBM) can differentiate into osteoclasts to resorb bone. This study was to identify PBM-expressed proteins significant for osteoporosis in Chinese Han elderly population (>65 years), and focused on two phenotypes of osteoporosis: low BMD and OF. METHODS: Label-free quantitative proteomics was employed to profile PBM proteome and to identify differentially expressed proteins (DEPs) between OF (N=27) vs. non-fractured (NF, N=24) subjects and between low BMD (N=12) vs. high BMD (N=12) subjects in women. Western blotting (WB) was conducted to validate differential expression, and ELISA to evaluate translational value for secretory protein of interest. RESULTS: We discovered 59 DEPs with fold change (FC)>1.3 (P<1×10-5), and validated the significant up-regulation of pyruvate kinase isozyme 2 (PKM2) with osteoporosis (P<0.001). PKM2 protein upregulation with OF was replicated with PBM in men (P=0.04). Plasma PKM2 protein level was significantly elevated with OF in an independent sample (N=100, FC=1.68, P=0.01). Pursuant functional assays showed that extracellular PKM2 protein supplement not only promoted monocyte trans-endothelial migration, growth, and osteoclast differentiation (marker gene expression), but also inhibited osteoblast growth, differentiation (ALP gene expression), and activity. CONCLUSION: The above findings suggest that PKM2 protein is a novel osteoporosis-associated functional protein in Chinese Han elderly population. It may serve as a risk biomarker and drug target for osteoporosis.

Effects of fermented herbal tea residue on meat quality, rumen fermentation parameters and microbes of black goats.

Herbal tea residue (HTR) is generally considered to be a reusable resource which has still retains considerable proportion of nutrients and active substances. This study aimed to investigate the effects of substitution of whole corn silage with fermented herbal tea residue (FHTR) on meat quality, serum indices, rumen fermentation, and microbes in Chuanzhong black goats. Twenty-two female Chuanzhong black goats (4 months old) with similar weight (9.55 ± 0.95 kg) were selected and randomly divided into two groups. FHTR was used to replace 0% (CON group) and 30% (FHTR group) of whole corn silage in the diets and fed as a total mixed ration (TMR) for Chuanzhong black goats. The adaptation feeding period was 7 days, and the experimental period was 35 days. Results illustrated that the FHTR group had higher value of a* and concentrations of DM and CP and lower rate of water loss (P < 0.05) than the CON group. For the serum indices, goats fed with 30% FHTR had higher (P < 0.05) concentration of CR on day 35. For rumen fermentation, the pH and ratio of acetic acid/propionic acid (AA/PA) in the FHTR group were significantly lower than those in the CON group (P < 0.05). In addition, we studied the goats's rumen microbial community composition and found that the dominant phyla were Firmicutes, Bacteroidetes,and Tenericutes; and the dominant genera were Quinella, Candidatus_Saccharimonas, and Saccharofermentans. There was a significant difference in the beta diversity of the rumen microbiota between groups (P < 0.05). To sum up, the addition of FHTR can affect the meat quality, serum indices, improved rumen fermentation by adjusted the diversity and function of the rumen microbiota.

Efficacy and Safety of Panax notoginseng Saponins in the Treatment of Adults With Ischemic Stroke in China: A Randomized Clinical Trial.

Importance: Preclinical and clinical studies have suggested the neuroprotective effect of Panax notoginseng saponins (Xuesaitong soft capsules). However, robust evidence in patients with ischemic stroke is lacking. Objective: To assess the efficacy and safety of Xuesaitong soft capsules in patients with ischemic stroke. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at 67 tertiary health centers in China from July 1, 2018, to June 30, 2020. Included patients were aged 18 to 75 years with a diagnosis of ischemic stroke and a National Institutes of Health Stroke Scale score between 4 and 15. Interventions: Eligible patients were randomly assigned within 14 days after symptom onset to receive either treatment with Xuesaitong soft capsules (120 mg orally twice daily) or placebo (120 mg orally twice daily) for 3 months. Main Outcomes and Measures: The primary outcome was functional independence at 3 months, defined as a modified Rankin Scale score of 0 to 2. Results: Among 3072 eligible patients with ischemic stroke who were randomized, 2966 (96.5%) were included in the modified intention-to-treat cohort (median [IQR] age, 62 [55-68] years; 1982 male [66.8%]). The number of patients who achieved functional independence at 3 months was 1328 (89.3%) in the Xuesaitong group and 1218 (82.4%) in the control group (odds ratio, 1.95; 95% CI, 1.56-2.44; P < .001). In the safety cohort, serious adverse events occurred in 15 of 1488 patients (1.0%) in the Xuesaitong group and 16 of 1482 (1.1%) in the control group (P = .85). Conclusions and Relevance: In this randomized clinical trial, Xuesaitong soft capsules significantly increased the likelihood of functional independence at 3 months in patients with ischemic stroke, indicating that this may be a safe and effective alternative therapy to improve prognosis in this population. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800016363.

Hypothermic neuroprotection by targeted cold autologous blood transfusion in a non-human primate stroke model.

Over decades, nearly all attempts to translate the benefits of therapeutic hypothermia in stroke models of lower-order species to stroke patients have failed. Potentially overlooked reasons may be biological gaps between different species and the mismatched initiation of therapeutic hypothermia in translational studies. Here, we introduce a novel strategy of selective therapeutic hypothermia in a non-human primate ischemia-reperfusion model, in which autologous blood was cooled ex vivo and the cool blood transfusion was administered at the middle cerebral artery just after the onset of reperfusion. Cold autologous blood cooled the targeted brain rapidly to below 34 °C while the rectal temperature remained around 36 °C with the assistance of a heat blanket during a 2-h hypothermic process. Therapeutic hypothermia or extracorporeal-circulation related complications were not observed. Cold autologous blood treatment reduced infarct sizes, preserved white matter integrity, and improved functional outcomes. Together, our results suggest that therapeutic hypothermia, induced by cold autologous blood transfusion, was achieved in a feasible, swift, and safe way in a non-human primate model of stroke. More importantly, this novel hypothermic approach conferred neuroprotection in a clinically relevant model of ischemic stroke due to reduced brain damage and improved neurofunction. This study reveals an underappreciated potential for this novel hypothermic modality for acute ischemic stroke in the era of effective reperfusion.

Effects of Fermented Herbal Tea Residue on Serum Indices and Fecal Microorganisms of Chuanzhong Black Goats.

Herbal tea residues (HTRs) are a by-product of herbal tea processing that contains many nutrients and active substances but are often discarded as waste. The main aim of the present study was to determine the food safety of HTRs and lay the foundation for its use as a novel feed resource for goats. In this study, discarded HTRs were fermented and then fed to 33 female Chuanzhong black goats (121 ± 4.00 days) with similar weight (9.33 ± 0.95 kg) and genetic background, which were divided into three groups (fermented herbal tea residue (FHTR) replacement of 0%, 15% and 30% of the forage component of the diet). The feeding experiment lasted for 35 days. On day 35, our findings indicated that the concentrations of hydroxyl radicals and urea increased linearly, and the concentrations of glutathione peroxidase increased quadratically with the increase in FHTR. In addition, we investigated the fecal microbiota composition of eight Chuanzhong black goats in the control, 15% and 30% FHTR replacement groups and found that FHTR had no remarkable effect on the fecal microbiota composition. Results indicated that goat physiological functions remained stable after FHTR was added to the diet.

Local anesthesia vs general anesthesia during endovascular therapy for acute posterior circulation stroke.

OBJECTIVE: The optimal anesthetic approach during endovascular therapy (EVT) in acute stroke patients remains an area of uncertainty. We investigated the impact of different anesthetic approaches on the outcome of posterior circulation stroke (PCS) patients undergoing EVT. METHODS: For this observational study, we enrolled consecutive PCS patients who underwent EVT from December 2012 to December 2018, and compared functional outcomes at 90 days as well as long-term follow-up in patients treated under local anesthesia (LA) versus general anesthesia (GA). Multivariable logistic regression and propensity score matched analyses were conducted. RESULTS: Among the 183 patients included in this study, 71 patients (38.8%) received LA and 112 patients (61.2%) received GA. Median modified Rankin Scale score at 90 days was 4 (IQR, 2-6) in both groups (P = .956). No significant differences in the rates of functional independence and mortality at 90 days as well as long-term follow-up post intervention were observed between the two groups, and Kaplan-Meier survival analysis showed comparable long-term survival probabilities. Safety outcomes (including procedure-related complications and serious adverse events) did not differ between these patients. The anesthetic approach was neither associated with functional independence nor associated with mortality. Propensity score matched analysis indicated similar results. CONCLUSIONS: For PCS patients undergoing EVT, LA compared with GA does not seem to result in different functional outcomes and complications rates.

General anesthesia vs local anesthesia during mechanical thrombectomy in acute ischemic stroke.

OBJECTIVE: To investigate the effect of general anesthesia (GA) on functional outcomes and complications rates in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT) compared to the use of local anesthesia (LA) at the puncture site. METHODS: This observational study was based on a prospectively registry study. AIS patients underwent MT with GA or LA from January 2013 to October 2017 were included. The primary outcome was the modified Rankin Scale (mRS) score at 90 days post-intervention. Furthermore, we assessed the long-term outcome of these patients. Multivariable logistic regression analysis was conducted to adjust for confounders. RESULTS: We enrolled 187 AIS patients in this study, patients in GA group had a similar mRS score compared to LA group at 90 days (2 [IQR, 1-4] vs 2.5 [IQR, 1-4], P = .917). No differences were found in the rates of functional independence (mRS 0-2), no or minimal disability (mRS 0-1), and mortality (mRS 6) between the 2 groups at 90 days post-intervention as well as long-term follow-up. The procedure-related complications and serious adverse events were similar between the LA group and GA group (P > .05 each). In multivariable analysis, GA use was not associated with functional outcomes. CONCLUSION: AIS patients who received GA during MT had similar functional outcomes and complications rates compared to patients received LA.

Killing of Staphylococcus aureus via Magnetic Hyperthermia Mediated by Magnetotactic Bacteria.

Staphylococcus aureus is a common hospital and household pathogen. Given the emergence of antibiotic-resistant derivatives of this pathogen resulting from the use of antibiotics as general treatment, development of alternative therapeutic strategies is urgently needed. Here, we assess the feasibility of killing S. aureus cells in vitro and in vivo through magnetic hyperthermia mediated by magnetotactic bacteria that possess magnetic nanocrystals and demonstrate magnetically steered swimming. The S. aureus suspension was added to magnetotactic MO-1 bacteria either directly or after coating with anti-MO-1 polyclonal antibodies. The suspensions were then subjected to an alternating magnetic field (AMF) for 1 h. S. aureus viability was subsequently assessed through conventional plate counting and flow cytometry. We found that approximately 30% of the S. aureus cells mixed with uncoated MO-1 cells were killed after AMF treatment. Moreover, attachment between the magnetotactic bacteria and S. aureus increased the killing efficiency of hyperthermia to more than 50%. Using mouse models, we demonstrated that magnetic hyperthermia mediated by antibody-coated magnetotactic MO-1 bacteria significantly improved wound healing. These results collectively demonstrated the effective eradication of S. aureus both in vitro and in vivo, indicating the potential of magnetotactic bacterium-mediated magnetic hyperthermia as a treatment for S. aureus-induced skin or wound infections.