Vitamin D as an intervention for improving quadriceps muscle strength in patients after anterior cruciate ligament reconstruction: study protocol for a randomized double-blinded, placebo-controlled clinical trial.

BACKGROUND: The goal of anterior cruciate ligament reconstruction (ACLR) is to restore the preinjury level of knee function to return to play (RTP). However, even after completing the rehabilitation programme, some patients may have persistent quadriceps muscle weakness affecting knee function which ultimately leads to a failure in returning to play. Vitamin D has been long recognized for its musculoskeletal effects. Vitamin D deficiency may impair muscle strength recovery after ACLR. Correcting vitamin D levels may improve muscle strength. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of vitamin D supplementation during the post-operative period on quadriceps muscle strength in anterior cruciate ligament (ACL)-injured patients. Patients aged 18-50 with serum vitamin D < 20 ng/ml, unilateral ACL injury, > 90% deficit in total quadriceps muscle volume on the involved leg compared with uninvolved leg, Tegner score 7 + , and no previous knee injury/surgery will be recruited. To assess patient improvement, we will perform isokinetic and isometric muscle assessments, ultrasound imaging for quadriceps thickness, self-reported outcomes, KT-1000 for knee laxity, biomechanical analysis, and Xtreme CT for bone mineral density. To investigate the effect of vitamin D status on quadriceps strength, blood serum samples will be taken before and after intervention. DISCUSSION: Patients with low vitamin D levels had greater quadriceps fibre cross-sectional area loss and impaired muscle strength recovery after ACL. The proposed study will provide scientific support for using vitamin D supplementation to improve quadriceps strength recovery after ACLR. TRIAL REGISTRATION: ClinicalTrials.gov NCT05174611. Registered on 28 November 2021.

Safe utilization of bioresources in gentamicin mycelial residues by thermal treatment: Antibiotic degradation, resistance gene inactivation and available nutrients promotion.

Gentamicin mycelium residues (GMRs) abundant in organic substances were generated during the production of gentamicin. Inappropriate handling techniques not only waste valuable resources, they could also result in residual gentamicin into the natural environment, leading to the generation of antibiotic resistance genes (ARGs), which would cause a significant threat to ecological system and human health. In the present work, the effects of thermal treatment on the removal of residual gentamicin in GMRs, as well as the changes of associated ARGs abundance, antimicrobial activity and bioresources properties were investigated. The results indicated that the hazards of GMRs was significantly reduced through thermal treatment. The degradation rate of residual gentamicin in GMRs reached 100 %, the total abundance of gentamicin resistance genes declined from 8.20 to 1.14 × 10-5 and the antibacterial activity of the decomposition products of GMRs on Vibrio fischeri was markedly reduced at 200 °C for 120 min. Additionally, the thermal treatment remarkably influenced the bioresource properties of GMRs-decomposition products. The release of soluble organic matters including soluble carbohydrates and soluble proteins have been enhanced in GMRs, while excessively high temperatures could lead to a reduction of nutrient substances. Generally, thermal treatment technology was a promising strategy for synergistic reducing hazards and utilizing bioresources of GMRs.

Conduction of a chemical structure-guided metabolic phenotype analysis method targeting phenylpropane pathway via LC-MS: Ginkgo biloba and soybean as examples.

The phenylpropane pathway (PPP) is one of the most extensively investigated metabolic routes. This pathway biosynthesizes many important active ingredients such as phenylpropanoids and flavonoids that affect the flavor, taste and nutrients of food. How to elucidate the metabolic phenotype of PPP is fundamental in food research and development. In this study, we designed a structural periodical table filled with 103 metabolites produced from PPP. All of them especially the 62 structural isomers were qualified and quantified with high resolution and sensitivity via multiple reaction mode in liquid chromatography tandem triple quadrupole mass spectrometry. Ginkgo biloba and soybean were used as samples for the practical application of this method: The delicate spatial-temporal metabolic balance of PPP from ginkgo biloba has been first elucidated; It is first confirmed that the salt and draught stresses could redirect the biosynthesis trend of PPP to produce more isoflavones in soybean leaves.

Mindfulness-Based Cognitive Therapy Regulates Brain Connectivity in Patients With Late-Life Depression.

Late-life depression (LLD) is an important public health problem among the aging population. Recent studies found that mindfulness-based cognitive therapy (MBCT) can effectively alleviate depressive symptoms in major depressive disorder. The present study explored the clinical effect and potential neuroimaging mechanism of MBCT in the treatment of LLD. We enrolled 60 participants with LLD in an 8-week, randomized, controlled trial (ChiCTR1800017725). Patients were randomized to the treatment-as-usual (TAU) group or a MBCT+TAU group. The Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were used to evaluate symptoms. Magnetic resonance imaging (MRI) was used to measure changes in resting-state functional connectivity and structural connectivity. We also measured the relationship between changes in brain connectivity and improvements in clinical symptoms. HAMD total scores in the MBCT+TAU group were significantly lower than in the TAU group after 8 weeks of treatment (p < 0.001) and at the end of the 3-month follow-up (p < 0.001). The increase in functional connections between the amygdala and middle frontal gyrus (MFG) correlated with decreases in HAMA and HAMD scores in the MBCT+TAU group. Diffusion tensor imaging analyses showed that fractional anisotropy of the MFG-amygdala significantly increased in the MBCT+TAU group after 8-week treatment compared with the TAU group. Our study suggested that MBCT improves depression and anxiety symptoms that are associated with LLD. MBCT strengthened functional and structural connections between the amygdala and MFG, and this increase in communication correlated with improvements in clinical symptoms. Randomized Controlled Trial; Follow-Up Study; fMRI; Brain Connectivity.

Effect of intracutaneous pyonex on analgesia and sedation in critically ill patients with mechanical ventilation.

The purpose of this study was to evaluate the effect of intracutaneous pyonex on analgesia and sedation in critically ill patients who underwent mechanical ventilation. A total of 88 critically ill patients were divided into a control group and an intervention group. Critical Care Pain Observation Tool (CPOT) and Richmond Agitation and Sedation Scale (RASS) were used to evaluate pain and agitation. The dosage and treatment period of sedative and analgesic drugs in the intervention group were notably lower than the control group (p < 0.05). Analgesia compliance time in the intervention group was superior to control group (p < 0.05). The shallow sedation compliance rate in the intervention group was significantly higher than the control group (p < 0.01). There was significant difference in blood gas analysis before and after treatment between the two groups (p < 0.05). After 2 h of sedation and analgesia, heart rate in the intervention group was lower than control group, but respiratory rate was higher than the control group (p < 0.05). The traditional analgesia and sedation combined with intracutaneous pyonex reduced the total amount and treatment period of sedative and analgesic drugs in critically ill patients throughout the treatment process, and it also decreased the adverse reactions such as blood pressure drops and respiratory depression.

Omega-3 polyunsaturated fatty acids ameliorated inflammatory response of mammary epithelial cells and mammary gland induced by lipopolysaccharide.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), essential fatty acids for humans and animals, have been reported to play a beneficial role in a variety of inflammatory diseases. In this study, we investigated the inhibitory effects and potential molecular mechanisms of n-3 PUFAs on the inflammatory response in lipopolysaccharide (LPS)-stimulated mammary alveolar cell line (MAC-T). Results showed that n-3 PUFAs could abate LPS-induced secretions of tumor necrosis factor-α, interleukin (IL)-6 and IL-1ß in MAC-T cells through the nuclear transcription factor kappa B (NF-κB) signal pathway. Meanwhile, n-3 PUFA intervention attenuated histopathologic changes of mammary glands, the white blood cell number decrease, and the alkaline phosphatase level decrease in the serum of mice challenged by LPS. Furthermore, n-3 PUFA intervention improved the ecological structure of the flora in terms of the structural disorder of the non-significant dominant flora induced by LPS in mice. Collectively, both in vitro and in vivo experiments revealed that n-3 PUFAs have a positive effect on LPS-induced inflammatory response, which was possibly mediated by the NF-κB signaling pathway and the intestinal microbiota.

Enhanced anti-amnestic effect of donepezil by Ginkgo biloba extract (EGb 761) via further improvement in pro-cholinergic and antioxidative activities.

ETHNOPHARMACOLOGICAL RELEVANCE: EGb 761 is a standardized dry extract of Ginkgo biloba L. leaves traditionally used by Eastern Asia and has been associated with beneficial effects on neurodegeneration disorders, including Alzheimer's disease. AIM OF THE STUDY: Since beneficial interactions between EGb 761 and donepezil have been observed in previous clinical studies, the current study was proposed aiming to further explore related mechanisms from both pharmacokinetics and pharmacodynamics aspects. MATERIALS AND METHODS: Pharmacodynamic interactions were studied in scopolamine-induced cognitive impairment rats received two-weeks treatment of vehicle, EGb 761 and/or donepezil by the Morris water maze test and ex vivo evaluation of biomarkers of cholinergic transmission and oxidative stress in rat brain. In the meantime, pharmacokinetic profiles of donepezil and bilobalide were obtained and compared among all treatment groups. In addition, impact of the bioavailable EGb 761 components on donepezil brain penetration was evaluated with the hCMEC/D3 cell monolayer model. RESULTS: Scopolamine-induced rats with co-treatment of EGb 761 and donepezil had significantly improved cognitive function in the Morris water maze test with increased brain levels of superoxide dismutase and decreased brain levels of acetylcholinesterase and malondialdehyde than that with treatment of only EGb 761 or donepezil. Despite such beneficial pharmacodynamics outcomes, the two-week co-treatment of EGb 761 and donepezil did not alter the plasma pharmacokinetics and brain uptake of donepezil or bilobalide, which was further verified in the hCMEC/D3 monolayer model. CONCLUSION: Co-administration of EGb 761 and donepezil exerted better anti-amnestic effect via further enhanced pro-cholinergic and antioxidative effects of EGb 761 or donepezil in scopolamine-induced cognitive impairment rat without alteration in their systemic/brain exposure.

The genome evolution and low-phosphorus adaptation in white lupin.

White lupin (Lupinus albus) is a legume crop that develops cluster roots and has high phosphorus (P)-use efficiency (PUE) in low-P soils. Here, we assemble the genome of white lupin and find that it has evolved from a whole-genome triplication (WGT) event. We then decipher its diploid ancestral genome and reconstruct the three sub-genomes. Based on the results, we further reveal the sub-genome dominance and the genic expression of the different sub-genomes varying in relation to their transposable element (TE) density. The PUE genes in white lupin have been expanded through WGT as well as tandem and dispersed duplications. Furthermore, we characterize four main pathways for high PUE, which include carbon fixation, cluster root formation, soil-P remobilization, and cellular-P reuse. Among these, auxin modulation may be important for cluster root formation through involvement of potential genes LaABCG36s and LaABCG37s. These findings provide insights into the genome evolution and low-P adaptation of white lupin.

Brain-Targeting Delivery of Two Peptidylic Inhibitors for Their Combination Therapy in Transgenic Polyglutamine Disease Mice via Intranasal Administration.

Polyglutamine diseases are a set of progressive neurodegenerative disorders caused by misfolding and aggregation of mutant CAG RNA and polyglutamin protein. To date, there is a lack of effective therapeutics that can counteract the polyglutamine neurotoxicity. Two peptidylic inhibitors, QBP1 and P3, targeting the protein and RNA toxicities, respectively, have been previously demonstrated by us with combinational therapeutic effects on the Drosophila polyglutamine disease model. However, their therapeutic efficacy has never been investigated in vivo in mammals. The current study aims to (a) develop a brain-targeting delivery system for both QBP1 and L1P3V8 (a lipidated variant of P3 with improved stability) and (b) evaluate their therapeutic effects on the R6/2 transgenic mouse model of polyglutamine disease. Compared with intravenous administration, intranasal administration of QBP1 significantly increased its brain-to-plasma ratio. In addition, employment of a chitosan-containing in situ gel for the intranasal administration of QBP1 notably improved its brain concentration for up to 10-fold. Further study on intranasal cotreatment with the optimized formulation of QBP1 and L1P3V8 in mice found no interference on the brain uptake of each other. Subsequent efficacy evaluation of 4-week daily QBP1 (16 µmol/kg) and L1P3V8 (6 µmol/kg) intranasal cotreatment in the R6/2 mice demonstrated a significant improvement on the motor coordination and explorative behavior of the disease mice, together with a full suppression on the RNA- and protein-toxicity markers in their brains. In summary, the current study developed an efficient intranasal cotreatment of the two peptidylic inhibitors, QBP1 and L1P3V8, for their brain-targeting, and such a novel therapeutic strategy was found to be effective on a transgenic polyglutamine disease mouse model.

[Mixed amanita phalloides poisoning with rhabdomyolysis: analysis of 4 cases].

We report the clinical characteristics, treatments and outcomes of 4 rare cases of mixed amanita fuliginea and amanita rimosa poisoning with rhabdomyolysis, and review the research progress in the intoxication mechanism and treatment. The latent time of amanita poisoning, defined as the period from the ingestion of poisonous mushroom to the onset of gastrointestinal symptoms, was about 8 days, and the severity of poisoning was associated with the amount of mushroom ingested. All the 4 patients developed multiple organ dysfunctions within 3 to 4 days after mushroom ingestion, predominantly in the liver, kidney and central nervous system accompanied with acute gastrointestinal injury and rhabdomyolysis. The treatment measures included persistent hemofiltration and intermittent hemoperfusion once daily for 5-7 days, and plasma exchange was administered in 2 cases for 1 or 2 times. High-dose vitamin C, glucose and corticosteroid were also given to the patients. After the treatments, two patients were cured and the other two died due to an excess intake of poisonous mushroom and lack of early preemptive therapies. Early emetic, gastric lavage, catharsis, fluid infusion and diuresis are critical to interrupt the enterohepatic circulation of amanita phalloides toxins and prevent the development of multiple organ dysfunction. Enhanced hemofiltration and sequential plasma therapy might effectively eliminate toxin from the blood to protect against further organ damages.

Inhibition of curcumin on influenza A virus infection and influenzal pneumonia via oxidative stress, TLR2/4, p38/JNK MAPK and NF-κB pathways.

Oxidative stress, Nrf2-HO-1 and TLR-MAPK/NF-κB signaling pathways have been proved to be involved in influenza A virus (IAV) replication and influenzal pneumonia. In the previous studies, we have performed several high-throughput drug screenings based on the TLR pathways. In the present study, through plaque inhibition test, luciferase reporter assay, TCID50, qRT-PCR, western blotting, ELISA and siRNA assays, we investigated the effect and mechanism of action of curcumin against IAV infection in vitro and in vivo. The results showed that curcumin could directly inactivate IAV, blocked IAV adsorption and inhibited IAV proliferation. As for the underlying mechanisms, we found that curcumin could significantly inhibit IAV-induced oxidative stress, increased Nrf2, HO-1, NQO1, GSTA3 and IFN-ß production, and suppressed IAV-induced activation of TLR2/4/7, Akt, p38/JNK MAPK and NF-κB pathways. Suppression of Nrf2 via siRNA significantly abolished the stimulatory effect of curcumin on HO-1, NQO1, GSTA3 and IFN-ß production and meanwhile blocked the inhibitory effect of curcumin on IAV M2 production. Oxidant H2O2 and TLR2/4, p38/JNK and NF-κB agonists could significantly antagonize the anti-IAV activity of curcumin in vitro. Additionally, curcumin significantly increased the survival rate of mice, reduced lung index, inflammatory cytokines and lung IAV titer, and finally improved pulmonary histopathological changes after IAV infection. In conclusion, curcumin can directly inactivate IAV, inhibits IAV adsorption and replication; and its inhibition on IAV replication may be via activating Nrf2 signal and inhibiting IAV-induced activation of TLR2/4, p38/JNK MAPK and NF-κB pathways.