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.

Investigation of the association between coffee and risk of RA-results from the Swedish EIRA study.

BACKGROUND: Studies on the association between coffee, a modifiable lifestyle factor, and rheumatoid arthritis (RA), a chronic autoimmune disease primarily affecting the joints, have been conflicting. The aim of the present study was to study the association between coffee consumption and risk of RA in the context of different lifestyle factors. METHODS: We included 2184 cases (72% women, mean age 55 years) newly diagnosed with RA during 2005-2018 in Sweden and 4201 controls matched on age, sex, and residential area. Data on coffee consumption was collected through a food frequency questionnaire and categorized into < 2 (reference), 2-< 4, 4-< 6, and ≥ 6 cups/day. We calculated odds ratios (OR) with 95% confidence intervals (CI) for coffee consumption and risk of RA, in a crude model (taking matching factors into account), and then adjusted first for smoking and further for BMI, educational level, alcohol consumption, and physical activity. We also stratified analyses on sex, smoking, rheumatoid factor, and anti-CCP2 status. RESULTS: In the crude model, high coffee consumption was associated with increased risk of RA (OR = 1.50, 95% CI 1.20-1.88 for ≥ 6 cups/day compared to < 2 cups). After adjusting for smoking, the OR decreased and was no longer statistically significant (OR = 1.16, 95% CI 0.92-1.46) and decreased further in the full model (OR = 1.14 95% CI 0.89-1.45). This pattern held true in all strata. CONCLUSION: The findings from this large, population-based case-control study did not support a significant association between coffee consumption and risk of RA as a whole nor within different subgroups.

Empathetic nursing with mindful cognitive therapy for fatigue, depression, and negative emotions in leukemia patients undergoing long-term chemotherapy.

BACKGROUND: Leukemia is a broad term for blood cell cancer. Leukemia is divided into acute or chronic, depending on cell differentiation. Leukemia patients are prone to adverse reactions during chemotherapy, such as anxiety, depression, and even suicide, affecting prognosis. As a nursing model developed by three well-known cognitive psychologists, empathetic nursing with mindfulness cognitive therapy (ENMCT) can effectively reduce anxiety and depression and improve the quality of life in patients with chronic disease. AIM: To explore the effect of ENMCT on cancer-induced fatigue, hope level, and negative emotions in patients with long-term leukemia chemotherapy. METHODS: A total of 103 patients with long-term leukemia chemotherapy diagnosed and treated in our hospital from July 2017 to October 2019 were enrolled and randomly assigned to observation and control groups using the random number table approach. Fifty-one patients in the control group received routine nursing, while 52 patients in the observation group received empathic nursing with mindfulness cognitive therapy. After three months of nursing care, cancer-induced fatigue was measured with the Piper Fatigue Scale (PFS), hope level with the Herth Hope Index (HHI), and negative emotion with the Hamilton Anxiety Scale (HAMA)/Hamilton Depression Scale (HAMD). Self-management (Chinese Strategies Used by People to Promote Health) was also recorded. RESULTS: The observation group's total scores in behavior, cognition, emotion, feeling, and PFS were lower than the control group after the intervention (P < 0.05). Keeping close contact with others, the attitude of taking positive actions, the attitude toward reality and future, and the total HHI score were higher in the observation group than the control group (P < 0.05). The observation group's HAMA and HAMD scores were lower than the control group (P < 0.05). The observation group's positive attitude, self-decision, and self-relief scores were greater than the control group (P < 0.05). CONCLUSION: Empathetic nursing with cognitive mindfulness therapy is beneficial in improving cancer-related fatigue, negative emotions, expectation level, and self-management ability in patients with long-term leukemia chemotherapy.

Protective effects of ginseng stem-leaf saponins on D-galactose-induced reproductive injury in male mice.

Panax ginseng is a perennial plant in the Araliaceae family. In this study, we investigated the protective effects of ginseng stem-leaf saponins (GSLS) isolated from P. ginseng against D-galactose-induced reproductive function decline, oxidative stress, and inflammatory response. Reproductive injuries were induced in mice via the subcutaneous injection of D-galactose (300 mg/kg) for six weeks. The mice were then treated with GSLS by intragastric administration. GSLS inhibited markers of oxidative stress and inflammatory cytokines induced by D-galactose in serum, liver and kidney, whereas GSLS increased the activities of antioxidant enzymes. Compared to the mice treated only with D-galactose, GSLS treatment significantly increased the average path velocity, straight line velocity, curvilinear velocity, and amplitude of the lateral head displacement of mouse sperm. Meanwhile, GSLS significantly increased the testosterone level and reduced the cortisol, FSH, and LH levels. Histopathological examination revealed alterations in the number and the arrangement of spermatogenic cells in the seminiferous tubules of the mice in the GSLS group. GSLS treatment suppressed MAPKs pathway activation in testes. These results suggest that GSLS can attenuate D-galactose-induced oxidative stress and inflammatory response in serum, liver and kidney, and ameliorate reproductive damage by inhibiting MAPKs signaling pathway.

Adverse effects of iron deficiency anemia on pregnancy outcome and offspring development and intervention of three iron supplements.

Iron deficiency anemia (IDA) is a common micronutrient deficiency among pregnant women with severe consequences including impaired immuno-inflammatory system, premature birth, fetal death etc. The present study aimed to investigate the effects of three iron supplements on IDA female rats and their offspring. The IDA female rat model was established with low iron diet and the rats were then mated. After pregnancy, rats were fed diets containing different iron supplements (iron polysaccharide complex, iron protein succinylate and ferrous sulfate) until their offspring were 42 days old. Pregnancy outcomes, haematological, iron metabolism, physical and neurological development indexes were determined. The results showed that all three iron supplements improved the levels of hematological parameters of both mother and offspring rats. After iron supplementation, serum iron, transferrin saturation and serum ferritin levels were increased compared with the IDA group. The level of ferritin light chain in the liver and spleen of both mother and offspring rats in iron supplemented groups was significantly higher than that of the IDA group. The average number of born alive per litter in the iron treatment groups was significantly higher than that in the IDA group. Iron supplements also improved the physical growth and neurobehavioral development of offspring rats. It was also found that iron supplementation improved the expression of ferritin light chain and the synaptic growth associated proteins in the brain and hippocampus. No significant difference was found in the efficacy of three iron supplements. These results suggest that pregnant and postpartum IDA affects pregnancy outcomes, offspring physical development and causes neural impairment. Sufficient iron supplementation can significantly improve IDA and its adverse effects on both mother and offspring.

Genistein inhibits nasopharyngeal cancer stem cells through sonic hedgehog signaling.

Genistein, a soy derived isoflavanoid compound, exerts anticancer effects in various cancers. Nasopharyngeal cancer stem cells (NCSCs) are a small subpopulation of cancer cells which are responsible for initiation, progression, metastasis, and recurrence of nasopharyngeal cancer. The present study aimed to investigate the suppressive effects of genistein on NCSCs and its underlying mechanism. NCSCs were enriched from human nasopharyngeal cancer cell lines CNE2 and HONE1 through tumorsphere-forming assay. It was shown that genistein inhibited the tumorsphere formation capacity, decreased the number of EpCAM+ cells, downregulated the expression of NCSCs markers, suppressed cell proliferation, and induced apoptosis of NCSCs. Genistein suppressed the activity of Sonic hedgehog (SHH) signaling, which was important for the maintenance of NCSCs, while activation of SHH signaling by purmorphamine diminished the inhibitory effects of genistein on NCSCs. Our data suggested that genistein inhibited NCSCs through the suppression of SHH signaling. These findings support the use of genistein for targeting NCSCs.

Accurate Analysis and Evaluation of Acidic Plant Growth Regulators in Transgenic and Nontransgenic Edible Oils with Facile Microwave-Assisted Extraction-Derivatization.

Determination of plant growth regulators (PGRs) in a signal transduction system (STS) is significant for transgenic food safety, but may be challenged by poor accuracy and analyte instability. In this work, a microwave-assisted extraction-derivatization (MAED) method is developed for six acidic PGRs in oil samples, allowing an efficient (<1.5 h) and facile (one step) pretreatment. Accuracies are greatly improved, particularly for gibberellin A3 (-2.72 to -0.65%) as compared with those reported (-22 to -2%). Excellent selectivity and quite low detection limits (0.37-1.36 ng mL(-1)) are enabled by fluorescence detection-mass spectrum monitoring. Results show the significant differences in acidic PGRs between transgenic and nontransgenic oils, particularly 1-naphthaleneacetic acid (1-NAA), implying the PGRs induced variations of components and genes. This study provides, for the first time, an accurate and efficient determination for labile PGRs involved in STS and a promising concept for objectively evaluating the safety of transgenic foods.

Practicality of intermittent fasting in humans and its effect on oxidative stress and genes related to aging and metabolism.

Caloric restriction has consistently been shown to extend life span and ameliorate aging-related diseases. These effects may be due to diet-induced reactive oxygen species acting to up-regulate sirtuins and related protective pathways, which research suggests may be partially inhibited by dietary anti-oxidant supplementation. Because caloric restriction is not sustainable long term for most humans, we investigated an alternative dietary approach, intermittent fasting (IF), which is proposed to act on similar biological pathways. We hypothesized that a modified IF diet, where participants maintain overall energy balance by alternating between days of fasting (25% of normal caloric intake) and feasting (175% of normal), would increase expression of genes associated with aging and reduce oxidative stress and that these effects would be suppressed by anti-oxidant supplementation. To assess the tolerability of the diet and to explore effects on biological mechanisms related to aging and metabolism, we recruited a cohort of 24 healthy individuals in a double-crossover, double-blinded, randomized clinical trial. Study participants underwent two 3-week treatment periods-IF and IF with anti-oxidant (vitamins C and E) supplementation. We found strict adherence to study-provided diets and that participants found the diet tolerable, with no adverse clinical findings or weight change. We detected a marginal increase (2.7%) in SIRT3 expression due to the IF diet, but no change in expression of other genes or oxidative stress markers analyzed. We also found that IF decreased plasma insulin levels (1.01 µU/mL). Although our study suggests that the IF dieting paradigm is acceptable in healthy individuals, additional research is needed to further assess the potential benefits and risks.

Safety and metabolic outcomes of resveratrol supplementation in older adults: results of a twelve-week, placebo-controlled pilot study.

Resveratrol has been found to have potent antioxidant, anti-inflammatory, and anticarcinogenic effects. The safety and efficacy of resveratrol supplementation in older adults are currently unknown. We conducted a double-blind, randomized, placebo-controlled trial to examine the safety and metabolic outcomes in 32 overweight, older adults (mean age, 73±7years). Participants were randomized into one of three treatment groups: (1) placebo, (2) moderate dose resveratrol (300mg/day), and (3) high dose resveratrol (1000mg/day). Both resveratrol and placebo were orally ingested in capsule form twice daily for 90days. Blood chemistry values remained within the normal range, and there were no significant differences in the number of participants reporting adverse events across conditions. Compared to placebo, glucose levels were significantly lower at post-treatment among participants randomized to both resveratrol conditions, with and without adjustment for the corresponding baseline values (ps<0.05). Glucose values of participants in the treatment groups, however, were not significantly different from baseline levels. These findings suggest that short-term resveratrol supplementation at doses of 300mg/day and 1000mg/day does not adversely affect blood chemistries and is well tolerated in overweight, older individuals. These findings support the study of resveratrol for improving cardio-metabolic health in older adults in larger clinical trials.

Effect of a novel dietary supplement on pH levels of healthy volunteers: a pilot study.

OBJECTIVE: To examine the effects of a greens alkalizing dietary supplement on urinary pH levels in individuals with lower-than-average pH levels. METHODS: The present study investigated the effects of an alkalizing formula (Reserveage Wholeganic Greens(TM)) on four individuals who had average urinary pH levels below 6.0 for three consecutive days. Following the three-day, baseline period, participants received Reserveage Wholeganic Greens(TM) for four consecutive days and were instructed to continue to measure their urine pH levels. Paired samples t-tests were used to examine pH levels before and after a four-day treatment period with Reserveage Wholeganic Greens(TM). RESULTS: Compared to baseline, mean urine pH levels in all volunteers were significantly higher following the supplementation with Reserveage Wholeganic Greens(TM) (5.89 ± 0.20 vs 5.56 ± 0.23; P<0.01). Participants' pH levels were also significantly higher than baseline on days 5, 6, and 7 of the treatment period (P < 0.05). Noteworthy, on day 7, participants' mean pH levels were significantly higher than at the beginning of the treatment period (6.03 ± 0.15 at day 7 vs 5.65 ± 0.24 at day 4; P < 0.01). CONCLUSION: The findings of this study suggest that supplementation with Reserveage Wholeganic Greens(TM) has an alkalizing effect on the body and can increase the urine pH levels in individuals with lower-than-average pH levels.

Treatment of relapsed precursor-B acute lymphoblastic leukemia with intensive chemotherapy: POG (Pediatric Oncology Group) study 9411 (SIMAL 9).

Pediatric patients who experience a bone marrow relapse of precursor-B acute lymphoblastic leukemia are cured <50% of the time. This study was designed to determine if intensification of therapies with known activity in this disease would improve the cure rates for patients with relapsed acute lymphoblastic leukemia. Patients were treated with intensive asparaginase during induction followed by repeated cycles of ifosfamide/etoposide and cytarabine/idarubicin. Patients with well-matched related donors were encouraged to undergo hematopoietic stem cell transplant as consolidation. The results of this study demonstrate no significant difference in disease-free survival in patients who received chemotherapy alone (45%) or chemotherapy followed by allogeneic stem cell transplant (50%). Furthermore, results from this study show no significant difference in event-free survival (39.9%±6.2%) or overall survival (41.6%±6.1%) at 8 years when compared with previous studies using less intensive regimens. Our results suggest that alternative therapies are needed to improve cure rates for pediatric patients with relapsed leukemia.

[Alleviation effects of LaCl3 on photosynthetic characteristics of cucumber seedlings under nitrate stress].

By the method of hydroponic culture, this paper studied the alleviation effects of LaCl3 on the photosynthetic characteristics of cucumber seedlings under nitrate (140 mmol NO3(-) x L(-1)) stress, with the related mechanisms discussed. Under nitrate stress, the seedlings leaf chlorophyll and carotenoids contents decreased significantly, and the leaf Mg2+-ATPase, Ca2+-ATPase activities also decreased. On the 7th day of nitrate stress, the decrease of seedlings photosynthetic rate was mainly due to stomatal limitation; but on the 12th day of nitrate stress, the decrease was mainly due to no-stomatal limitation. Supplement with LaCl3 could make the cucumber seedlings keep relatively higher leaf Mg2+-ATPase and Ca2+-ATPase activities and chlorophyll and carotenoids contents, and applying 20 micromol x L(-1) of LaCl3 could increase the carotenoids content significantly. LaCl3 could also improve the leaf gas exchange, and alleviate the decrease of leaf Fv/Fm, PhiPSII, AQY, CE, and qp under nitrate stress, which helped the leaves making good use of light energy and maintaining higher CO2 assimilation capacity. An additional 20 micromol x L(-1) of LaCl3 could alleviate the nitrate stress on the photosynthesis of cucumber seedlings efficiently, but an additional 200 micromol x L(-1) of LaCl3 only had the alleviation effect at the initial period of nitrate stress. Our results could benefit to the improvement of greenhouse soil.

A novel synthetic oleanolic acid derivative with amino acid conjugate suppresses tumour growth by inducing cell cycle arrest.

Oleanolic acid (3beta-hydroxy-olean-12-en-28-oic acid; OA) has a wide variety of bioactivities and is used for medicinal purposes in many Asian countries. Various derivatives of OA have been synthesized in attempts to improve the potency. Here we describe the anti-tumour activity of a novel OA derivative, N-[(3beta)-3-(acetyloxy)-28-oxoolean-12-en-28-yl]-glycine methyl ester (AOA-GMe). AOAGMe was a more potent inhibitor of the growth of B16 melanoma cells than its parent compound OA, both in-vitro and in-vivo. AOA-GMe also exhibited dose-dependent inhibition of human K562 leukaemia cells, but had almost no toxicity in normal human peripheral blood mononuclear cells. AOA-GMe induced cell cycle arrest in G0/G1 and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D, cyclin-dependent kinase CDK4 and phosphorylated retinoblastoma protein, and increases in the cyclin-dependent kinase inhibitor p15. OA did not show such activities. These results suggest that AOA-GMe may induce growth arrest in tumour cells through regulation of proteins involved in the cell cycle.