From immune checkpoints to therapies: understanding immune checkpoint regulation and the influence of natural products and traditional medicine on immune checkpoint and immunotherapy in lung cancer.

Lung cancer is a disease of global concern, and immunotherapy has brought lung cancer therapy to a new era. Besides promising effects in the clinical use of immune checkpoint inhibitors, immune-related adverse events (irAEs) and low response rates are problems unsolved. Natural products and traditional medicine with an immune-modulating nature have the property to influence immune checkpoint expression and can improve immunotherapy's effect with relatively low toxicity. This review summarizes currently approved immunotherapy and the current mechanisms known to regulate immune checkpoint expression in lung cancer. It lists natural products and traditional medicine capable of influencing immune checkpoints or synergizing with immunotherapy in lung cancer, exploring both their effects and underlying mechanisms. Future research on immune checkpoint modulation and immunotherapy combination applying natural products and traditional medicine will be based on a deeper understanding of their mechanisms regulating immune checkpoints. Continued exploration of natural products and traditional medicine holds the potential to enhance the efficacy and reduce the adverse reactions of immunotherapy.

The Maternal Donor of Chrysanthemum Cultivars Revealed by Comparative Analysis of the Chloroplast Genome.

Chrysanthemum (Chrysanthemum morifolium Ramat) is an important floricultural crop and medicinal herb. Modern chrysanthemum cultivars have complex genetic backgrounds because of multiple cycles of hybridization, polyploidization, and prolonged cultivation. Understanding the genetic background and hybrid origin of modern chrysanthemum cultivars can provide pivotal information for chrysanthemum genetic improvement and breeding. By now, the origin of cultivated chrysanthemums remains unclear. In this study, 36 common chrysanthemum cultivars from across the world and multiple wild relatives were studied to identify the maternal donor of modern chrysanthemum. Chloroplast (cp) genomes of chrysanthemum cultivars were assembled and compared with those of the wild relatives. The structure of cp genomes was highly conserved among cultivars and wild relatives. Phylogenetic analyses based on the assembled cp genomes showed that all chrysanthemum cultivars grouped together and shared 64 substitutions that were distinct from those of their wild relatives. These results indicated that a diverged lineage of the genus Chrysanthemum, which was most likely an extinct or un-sampled species/population, provided a maternal source for modern cultivars. These findings provide important insights into the origin of chrysanthemum cultivars, and a source of valuable genetic markers for chrysanthemum breeding programs.

The effects on pain, physical function, and quality of life of quadriceps strengthening exercises combined with Baduanjin qigong in older adults with knee osteoarthritis: a quasi-experimental study.

BACKGROUND: Exercise is recommended as a principal treatment for individuals with knee osteoarthritis (KOA). However, the best choice for an optimal exercise program able to promote long-term compliance in KOA patients is not clear. This study aims to compare the effect of combined exercise (CE: quadriceps strengthening exercises (QSE) and Baduanjin qigong training (BDJ)) versus QSE alone and BDJ alone on older adults with KOA. METHODS: A three-arm, quasi-experimental trial with repeated measurements was used. As a cluster randomized trial, participants from three community centers were assigned respectively to QSE group, BDJ group and CE group. We assessed pain intensity, physical function, self-efficacy, and health-related quality-of-life (HRQoL) using standardized instruments at baseline, 3 months and 6 months follow-up. RESULTS: One hundred and twenty-eight participants with KOA aged over 60 completed the study. Over the 6 months, there were significant group interaction effects on pain intensity (F = 28.888, P < 0.001), physical function (F = 26.646, P < 0.001), and self-efficacy (F = 22.359, P < 0.001), and, based on a short form-12 item health survey questionnaire (SF-12), physical component summary (F = 7.470, P < 0.001), and mental component summary (F = 10.207, P < 0.001). Overall, the CE group exhibited significantly greater improvement in all outcomes when compared to the QSE group and the BDJ group. CONCLUSIONS: CE treatment is more effective than QSE and BDJ in pain relief, increasing physical function, improving self-efficacy, and raising quality-of-life in community-dwelling KOA older adults. Moreover, it promotes long-term compliance in KOA community patients. TRIAL REGISTRATION: Chinese Clinical Trails Registry number ChiCTR2000033387 (retrospectively registered). Registered 30 May 2020.

The comparison of the effects of local cooling and heating on apoptosis and pyroptosis of early-stage pressure ulcers in rats.

The exploration of an effective method for preventing and treating pressure ulcers (PUs) is a hot topic in medical research. Recently, disputes about the choice of heat and cold therapies have emerged for the prevention and treatment of clinical PUs. The present study was designed to compare the effect of cool and heat therapies on pyroptosis and apoptosis of early-stage PUs in rats. Sixty SD rats of SPF grade were randomly divided into the sham group, model group, heating group, and cooling group. We established a rat model of early-stage PUs by using an ischemia-reperfusion method. At the end of the experiment, the tissue underneath the compressed region was collected for hematoxylin and eosin staining, transmission electron microscopy, immunohistochemistry, immunofluorescence staining, a TdT-mediated dUTP nick-end labeling assay, a Western blot analysis, and a mitochondrial swelling experiment. Our results suggested that the mitochondrial apoptotic pathway and pyroptosis were involved in the formation of early-stage PUs, and local heating increased the PU injury in rats, while local cooling reduced the PU injury in rats. This study showed that heat therapy might not be suitable for the clinical treatment and care of early-stage PUs, while cold therapy may be more appropriate.

The effect of Baduanjin qigong combined with CBT on physical fitness and psychological health of elderly housebound.

BACKGROUND: To investigate the effectiveness of Baduanjin qigong combined with cognitive-behavior therapy (CBT) on the physical fitness and psychological health of elderly housebound. MATERIALS AND METHODS: The 120 elderly housebound were randomly divided into 3 intervention groups: Baduanjin training, Baduanjin training combined with CBT, and CBT. The interventions were conducted by means of home visits over 6 months. Spirometry, SF-36 health survey of quality of life, and Lawton and Brody Instrumental Activities of Daily Living Scale (IADL) were used to collect physical health data, and self-evaluation of overall health status, self-evaluation of loneliness, and short-form geriatric depression scale (GDS-15) were used to collect mental health data at baseline, 3 months, and 6 months after intervention. Data was analyzed by repeated measures analysis of variance (rANOVA) and chi-squared test (χ test). RESULTS: Forced vital capacity (FVC), maximum voluntary ventilation (MVV), quality of life (QOL), and self-reported health status were significantly increased (P < .05) in the group receiving joint Baduanjin and CBT intervention at 3 months and 6 months, as compared to the Baduanjin only group or the CBT only group. Activities of daily living (ADL), self-evaluated loneliness, and level of depression were significantly lowered (P < .05) in the group receiving joint Baduanjin and CBT intervention at 3 months and 6 months, as compared to the Baduanjin only group or the CBT only group. CONCLUSIONS: Physical and psychological statuses of elderly housebound were significantly improved by Baduanjin training combined with CBT. The effect of the combined intervention exceeded that of CBT or Baduanjin alone.

Molecular mechanism of Hoxd13-mediated congenital malformations in rat embryos.

OBJECTIVE: To investigate the molecular mechanism of Hoxd13-mediated congenital malformations in rat embryos. METHODS: SD female rats were mated with male rats in a 1:1 mating scheme. Thirty pregnant female rats were randomly divided into three groups: the control group receiving a normal diet, the model group receiving a vitamin A-deficient diet, and the treatment group receiving a vitamin A-deficient diet supplemented with pcDNA-Hoxd13. The expression of Hoxd13 mRNA and protein in normal embryonic tissue and congenital malformations was determined by RT-PCR and Western blot analysis. At day 20, rats were dissected, and the fetal weight, body and tail length, and the number of live births, absorbed fetus, and stillbirth in each group were recorded. Wnt and Slim1 expression was detected by RT-PCR and Western blot analysis. ß-catenin and c-myc expression was also quantified by Western blot analysis. RESULTS: The expression of Hoxd13 mRNA and protein in congenital malformations was significantly lower compared with normal embryonic tissue (P<0.01). The administration of exogenous Hoxd13 in the treatment group markedly increased the fetal weight, body and tail length (P<0.05), improved the embryonic survival rate, and reduced the embryonic resorption rate and stillbirth rate (P<0.05). Exogenous Hoxd13 markedly promoted the expression of Wnt2, Wnt5a, Wnt7b and Slim1 protein and mRNA (P<0.01), and the expression of ß-catenin and c-myc protein in congenital malformations (P<0.01). CONCLUSION: Hoxd13 expression was decreased in rat embryos with congenital malformations. The administration of exogenous Hoxd13 alleviated fetal malformation probably through stimulation of Slim1 expression and Wnt/ß-catenin signaling pathway.