Microwave-responsive gadolinium metal-organic frameworks nanosystem for MRI-guided cancer thermotherapy and synergistic immunotherapy.

The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events. Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect. Herein, we designed a Gd-based metal-organic framework (Gd-MOF) nanosystem for MRI-guided thermotherapy and synergistic immunotherapy, which featured high performance in drug loading and tumor tissue penetration. The PD-1 inhibitor (aPD-1) was initially loaded in the porous Gd-MOF (Gd/M) nanosystem. Then, the phase change material (PCM) and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM (Gd/MPC). When entering the tumor microenvironment (TME), Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness, improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1. Meanwhile, Gd/MPC can be used for contrast-enhanced MRI. Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun, and ultimately leads to the apoptosis of cancer cells after treatment. In general, Gd/MPC nanosystem not only solves the problem of system side effect, but also achieves the controlled drug release via PCM, providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.

[Therapeutic effect and mechanism of Mailuo Shutong Pills on posterior limb swelling caused by femur fracture in rats based on intestinal flora and intestinal metabolism].

This study aimed to investigate the protective effect and underlying mechanism of Mailuo Shutong Pills(MLST) on posterior limb swelling caused by femur fracture in rats. The rats were randomly divided into a sham operation group, a model group, a low-dose MLST group(1.8 g·kg~(-1)·d~(-1)), a high-dose MLST group(3.6 g·kg~(-1)·d~(-1)), and a positive drug group(60 mg·kg~(-1)·d~(-1) Maizhiling Tablets). The femur in the sham operation group was exposed and the wound was sutured, while the other four groups underwent mechanical damage to cause femur fracture. The rats were treated with corresponding drugs by gavage 7 days before modeling and 5 days after modeling, while those in the sham operation group and the model group were given an equivalent dose of distilled water by gavage. Hematoxylin-eosin(HE) staining was used to detect the pathological injury of the posterior limb muscle tissues in rats, and the degree of hind limb swelling was measured. The enzyme-linked immunosorbent assay(ELISA) kit was used to detect the expression levels of interleukin-6(IL-6), interleukin-1ß(IL-1ß), and tumor necrosis factor-α(TNF-α) in the serum of rats in each group. The activity of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and glutathione peroxidase(GSH-Px) in rat serum was also measured. Western blot was used to detect the protein expression levels of heme oxygenase 1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), and nuclear transcription factor E2-related factor 2(Nrf2) in rat posterior limb muscle tissues. The changes in the intestinal flora and intestinal metabolites in rats were detected by 16S rDNA sequencing and ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS), respectively, to explore the underlying mechanism of MLST in treating posterior limb swelling caused by femur fracture in rats. Compared with the model group, MLST significantly improved the degree of posterior limb swelling in rats, reduced the levels of serum inflammatory factors, and alleviated oxidative stress injury. The HE staining results showed that the inflammatory infiltration in the posterior limb muscle tissues of rats in the MLST groups was significantly improved. Western blot results showed that MLST significantly increased the protein expression of HO-1, NQO1, and Nrf2 in rat posterior limb muscle tissues compared with the model group. The 16S rDNA sequencing results showed that MLST improved the disorder of intestinal flora in rats after femur fracture. The UPLC-MS/MS results showed that MLST significantly affected the bile acid biosynthesis and metabolism pathway in the intestine after femur fracture, and the Spearman analysis confirmed that the metabolite deoxycholic acid involved in bile acid biosynthesis was positively correlated with the abundance of Turicibacter. The metabolite cholic acid was positively correlated with the abundance of Papilibacter, Staphylococcus, and Intestinimonas. The metabolite lithocholic acid was positively correlated with Papilibacter and Intestinimonas. The above results indicated that MLST could protect against the posterior limb swelling caused by femur fracture in rats. This protective effect may be achieved by improving the pathological injury of the posterior limb muscle, reducing the expression levels of inflammatory and oxidative stress-related factors in serum, reducing the oxidative injury of the posterior limb muscle, improving intestinal flora, and balancing the biosynthesis of bile acids in the intestine.

Operational and Intervention Effects of Targeted Tuina in Lumbar Intervertebral Disc Degeneration Model Rabbits.

Tui Na or massage therapy alleviates symptoms related to intervertebral disc degeneration (IDD). However, precise, repeatable, standardized instructions for Tuina manipulation are lacking. This study establishes IDD model rabbits induced by fibrous ring puncture, creates targeted Tuina stimulation protocols at the acupuncture points in the lumbar region, and describes in detail the operation methods and requirements of kneading, pointing, and flicking. New Zealand male white rabbits (n = 15) were selected and randomly divided into a blank group, a model group, and a Tuina group. The rabbits in the model group and the Tuina group were molded by fibrous ring puncture; the rabbits in the model group were only immobilized on the operating table without treatment. In contrast, the Tuina group used the "8N/10N, 30 cycles/min" prescription for kneading, pointing, and flicking to perform the intervention, using tactile sensory aids to monitor and regulate the intensity of the Tuina operation. Imaging diagnosis and pathological tests were used to assess the effect of Tuina in rabbits, and the results showed improved imaging features and significantly lowered pathology scores of lumbar disc degeneration in the Tuina group compared to the model group (P < 0.01). Targeted Tuina in the lumbar region may be beneficial in the alleviation of lumbar disc degeneration, but further verification is needed. By regularly performing Tuina and recording the mechanical information involved enables reproducible manipulation prescriptions and helps to observe the basic features of the underlying mechanism of Tuina for IDD.

[Conversion of traditional Chinese medicine (TCM) into nanomedicine:application of theory of unification of medicines and excipients].

In recent years, the use of active substances as excipients or as substitutes for other excipients in the design of modern drug delivery systems has received widespread attention, which has promoted the development of the theory of unification of medicines and excipients in the design of traditional Chinese medicine(TCM) preparations. Adopting the theory of unification of medicines and excipients to design drug delivery systems can reduce the use of excipients and thus the cost of preparations, reduce drug toxicity, increase drug solubility and biocompatibility, enhance synergistic effect, and realize targeted delivery and simultaneous delivery of multiple components. However, the research on the application of this theory in the modern drug delivery system of TCM preparations is still insufficient, with few relevant articles. In addition, the TCM active substances that can be used as the excipients remain to be catalogued. In this paper, we review the types and applications of the drug delivery systems with TCM active substances as excipients and describe their common construction methods and mechanisms, aiming to provide references for the in-depth research on the modern drug delivery systems for TCM preparations.

[Nutrition Plays a Vital Role in the Prevention and Treatment of COVID-19].

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an ongoing global pandemic of coronavirus disease 2019 (COVID-19). Proper nutritional support helps boost the immunity of the human body, strengthen the high-risk populations' defense against SARS-CoV-2, reduce the prevalence of COVID-19, prevent mild cases from developing into severe cases, and reduce the occurrence of adverse symptoms during recovery. Nutritional support is an important guarantee to provide protection against virus infection, promote patient recovery, and improve patient prognosis. Whole nutritional food formulas designed according to the characteristic clinical symptoms of COVID-19 provide patients with comprehensive nutritional support of appropriate nutritional content, which effectively improves the nutritional status of patients and provides strong technical support to improve their quality of survival. During the critical period of COVID-19 prevention and control, more emphasis should be placed on the essential role of nutritional support and the clinical efficacy of nutritional support should be given full play.

Astragalus polysaccharide (APS) supplement in beagle dogs after castration: Effects on the haematology and serum chemistry profiles, immune response, and oxidative stress status.

BACKGROUND: Castration is one of the most common surgical procedures performed in dogs. However, based on increasing evidence, male animals experience significant pain after castration. Astragalus polysaccharide (APS), one of the main bioactive components in A. membranaceus bunge, has been widely used as part of Fu-Zheng therapy to enhance natural defense mechanisms. INTRODUCTION: This study was carried out to determine the effects of supplementing different doses of Astragalus polysaccharide (APS; control, 0 mg/kg; APSL, 400 mg/kg; and APSH, 800 mg/kg) for 8 weeks on the haematology and serum chemistry profiles, immune response, and oxidative stress status in weanling beagle dogs. METHODS: After adapting to the experimental environment for 1 week, 18 male beagle dogs (Sichuan Institute of Musk Deer Breeding, China; average initial weight, 3.80 ± 0.43 g; age, 3-month-old) were randomly allotted to diets supplemented with three doses of APS (Control, 0 mg/kg; low, 400 mg/kg; and high, 800 mg/kg), referred to as control, APSL, and APSH, respectively; six dogs were assigned to each treatment. The dogs were fed the respective diets twice daily at 08:30 and 16:30 h in sufficient quantity to supply the metabolizable energy requirements for 8 weeks. On day 43 (19 weeks old), the dogs were castrated. On days 42 (prior to castration, 19 weeks old), 50 (day 7 after castration, 20 weeks old), and 57 (day 14 after castration, 21 weeks old) to measure the haematology, blood chemistry, immune response, and oxidative stress status parameters. RESULTS: Based on our findings, the APSH diet decreased weight gain and increased the feed to gain ratio in dogs (P < 0.05). At 14 days after castration, the wound was almost closed, slightly swollen, dry, and clean in the groups supplemented with APS. In addition, optimal APS supplementation was found to decrease erythrocyte count (RBC), haematocrit (HCT), alkaline phosphatase (ALP), alanine aminotransferase (ALT), C-reactive protein (CRP), interleukin 1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) levels, and cortisol and protein carbonyl (PC) concentrations (P < 0.05). Moreover, the mean corpuscular haemoglobin (MCH) and platelet (PLT) levels, interleukin 10 (IL-10) and glutathione (GSH) content, and Cu/Zn superoxide dismutase (SOD1), catalase (CAT), and glutathione peroxidase (Se-GPx) activities were increased in the APS supplemented groups (P < 0.05) CONCLUSION: This study demonstrated that supplementing weanling beagle dogs with optimum APS could positively affect wound healing by improving their haematological profile (decreased RBC and HCT content, increased MCH and PLT levels), serum biochemical parameters (decreased ALP and ALT content), immune status (decreased CRP, IL-1ß, and TNF-α levels; increased IL-10 content), and antioxidant defense (decreased cortisol and PC content; increased GSH content, and SOD1, CAT, and Se-GPx activities). However, the detailed mechanism whereby APS regulates these changes requires further investigation. In addition, the results of this study suggest that 400 mg/kg diet is the optimum APS dose for beagle dogs.

[Therapeutic effect of Jingfang Granules on CCl_4-induced liver fibrosis in mice and its mechanism].

To investigate the therapeutic effect of Jingfang Granules on carbon tetrachloride(CCl_4)-induced liver fibrosis in mice and its mechanism. Forty-nine 8-week-old male C57 BL/6 J mice were randomly divided into a blank group, a CCl_4 group, a silybin group(positive control, 100 mg·kg~(-1))+CCl_4, a Jingfang high-dose(16 g·kg~(-1)) group, a Jingfang high-dose(16 g·kg~(-1))+CCl_4 group, a Jingfang medium-dose(8 g·kg~(-1))+CCl_4 group, and a Jingfang low-dose(4 g·kg~(-1))+CCl_4 group, with 7 mice in each group. The mice in the blank group and Jingfang high-dose group were intraperitoneally injected olive oil solution, and mice in other groups were intraperitoneally injected with 10% CCl_4 olive oil solution(5 mL·kg~(-1)) to induce liver fibrosis, twice a week with an interval of 3 d, for 8 weeks. At the same time, except for the blank group and CCl_4 group, which were given deionized water, the mice in other groups were given the corresponding dose of drugs by gavage once daily for 8 weeks with the gavage volume of 10 mL·kg~(-1). All mice were fasted and freely drank for 12 h after the last administration, and then the eyeballs were removed for blood collection. The liver and spleen were collected, and the organ index was calculated. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bile acid(TBA), and triglyceride(TG) in the serum of mice were detected by an automated analyzer. Tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and interleukin-1ß(IL-1ß) levels were detected by enzyme-linked immunosorbent assay(ELISA). Kits were used to detect the contents of superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the liver tissue. Pathological changes in the liver tissue were observed by hematoxylin-eosin(HE), Masson, and Sirius red staining. Western blot was used to detect protein expressions of transforming growth factor-ß(TGF-ß), α-smooth muscle actin(α-SMA) and Smad4 in the liver tissue. The results indicated that Jingfang Granules significantly reduced the organ index, levels of ALT, AST, TBA,TG, TNF-α, IL-6, and IL-1ß in the serum, and the content of MDA in the liver tissue of mice with CCl_4-induced liver fibrosis. Jingfang Granules also significantly increased the content of SOD and GSH in the liver tissue. Meanwhile, Jingfang Granules down-regulated the protein levels of TGF-ß, α-SMA, and Smad4. Furthermore, Jingfang Granules had no significant effect on the liver tissue morphology and the above indexes in the normal mice. In conclusion, Jingfang Granules has obvious therapeutic effect on CCl_4-induced liver fibrosis, and its mechanism may be related to reducing the expression of pro-inflammatory factors, anti-oxidation, and regulating TGF-ß/Smad4 signaling pathway.

[Intervention effect of Jingfang Mixture on urticaria mice based on NF-κB/NLRP3/IL-1ß signaling pathway].

This study explored the curative effect of Jingfang Mixture on urticaria mice induced by aluminum hydroxide/ovalbumin, and discussed its mechanism. Sixty male Kunming mice were randomly divided into a normal group, a model group, three Jingfang Mixture(low-dose, medium-dose, and high-dose) groups, and a positive drug(cetirizine hydrochloride) group. The urticarial model in mice was induced by the intraperitoneal injection of the mixed solution of ovalbumin and aluminum hydroxide. The degrees of pruritus were observed after the second immunization. Pathological changes were detected by hematoxylin and eosin(HE) staining. Levels of interleukin 1ß(IL-1ß) and tumor necrosis factor α(TNF-α) in the serum were detected by enzyme linked immunosorbent assay(ELISA). Expressions of NOD-like receptor protein 3(NLRP3) and IL-1ß were detected by immunohistochemistry(IHC). Expressions of nuclear factor kappa-B(NF-κB p65), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), cysteinyl aspartate-specific proteases 1(caspase-1), and IL-1ß proteins were detected by Western blot. The results showed that, except for the normal group, the mice in all groups had different degrees of pruritus. Compared with the model group, the Jingfang Mixture groups and the positive drug group prolonged the scratching latency of mice(P<0.05), and significantly reduced the number of scratching(P<0.05). In addition, the Jingfang Mixture groups and the positive drug group improved the pathological morphology of skin tissue. The expression levels of IL-1ß and TNF-α in serum were significantly reduced(P<0.05), and the number of NLRP3 and IL-1ß positive cells was decreased(P<0.01). The expressions of p-NF-κB p65, NLRP3, ASC, cleaved caspase-1, and IL-1ß protein were significantly down-regulated(P<0.05). The results of the above study indicate that Jingfang Mixture inhibit the inflammatory response in urticaria mice, and the mechanism may be related to the inhibition of activating NF-κB/NLRP3/IL-1ß signaling pathway.

[Mechanism of pathogenesis of Jingfang Mixture in intervention of chronic spontaneous urticaria based on serum metabolomics].

This study aims to clarify the effect of Jingfang Mixture on the treatment of chronic urticarial and its mechanism, and investigate the regulatory effect of chronic urticaria on the metabolic disorder of endogenous metabolites in the blood. The mice were randomly divided into normal group, model group, and Jingfang Mixture group, and modeling and administration continued for 21 d. The changes in endogenous small molecules in rat serum were determined by ultra-high performance liquid chromatography-electrospray ionization-Q Exactive-Orbitrap-mass spectrometry(UHPLC-ESI-QE-Orbitrap-MS) metabolomics technology. The change trend of endogenous metabolites in rat serum was analyzed to find potential biomarkers. The results showed that Jingfang Mixture regulate 16 biomarkers, mainly including taurine, glutamate, succinic acid, docosahexaenoic acid, and arachidonic acid. Metabolic pathway analysis was carried out by MetaboAnalyst, and P<0.01 was taken as the potential key metabolic pathway. Ten metabolic pathways were closely related to the treatment of chronic urticarial by Jingfang Mixture, mainly involved in the glutamate metabolism, taurine and hypotaurine metabolism, arginine and proline metabolism, arachidonic acid metabolism, tricarboxylic acid cycle, unsaturated fatty acid biosynthesis, glutathione metabolism, phenylalanine metabolism, alanine, aspartic acid, and glutamate metabolism, and butyric acid metabolism. Glutamate metabolism and butyric acid metabolism involved more metabolic pathways than others. Therefore, it was speculated that Jingfang Mixture had a balanced regulating effect on the related metabolic pathways which caused the serum disorder in the rats with urticaria, and tended to regulate the metabolic differential to the normal level in the rats with urticaria. This paper provides references for studying the mechanism of Jingfang Mixture from the perspective of endogenous metabolites and metabolic pathways in vivo. At the same time, the endogenous substances explored in this paper can be used as important biomarkers for the prevention of urticaria.

Antibiotic-impregnated calcium sulfate for the treatment of pediatric hematogenous osteomyelitis.

BACKGROUND: Antibiotic-impregnated calcium sulfate has excellent curative efficacy in chronic osteomyelitis. However, its curative efficacy in pediatric hematogenous osteomyelitis has not been sufficiently studied. The purpose of this study was to evaluate the curative effects of antibiotic-impregnated calcium sulfate in the treatment of pediatric hematogenous osteomyelitis. METHODS: Overall, twenty-one pediatric patients with hematogenous osteomyelitis treated at our hospital between 2013 and 2018 were included for assessment. The clinical history, clinical manifestation, infection recurrence rate, sinus leakage, incision leakage, pathological fractures, bone growth and surgical procedures were analyzed. RESULTS: The infection recurrence rate was 0% (0/21) at a minimum of 31 months (range 31 to 91 months) of follow-up. Postoperative incision leakage was found in one pediatric patient. Osteolysis was found in one pediatric patient. Acceleration of bone growth occurred in one pediatric patient. Retardation of bone growth occurred in one pediatric patient. Genu valgus deformity occurred in one pediatric patient. CONCLUSIONS: Although noninfectious complications occurred, the curative effect of antibiotic-impregnated calcium sulfate in pediatric hematogenous osteomyelitis was satisfactory.

Chemical Constituents from Mushroom Suillus luteus (Agaricomycetes) and Their Bioactivities.

Wild edible mushrooms are a huge source to discover bioactive natural products. In this work, one new polyprenylphenol derivative, termed 2-geranylgeranyl-1,4-benzenediol 1-O-acetate (1), together with eight known compounds (2-9) were isolated from wild edible mushroom Suillus luteus. The structure of new compound was elucidated by high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance data. The structures of known compounds were elucidated by comparison of their nuclear magnetic resonance data with literature data. Compounds 1-7 exhibited significant 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity with IC50 values ranging from 1.55 ± 0.29 to 19.89 ± 2.28 µM. In addition, compounds 1-7 also showed tyrosinase inhibitory activity with IC50 values ranging from 21.97 ± 3.74 to 66.26 ± 6.85 µM.

Abundant and diverse endophytic bacteria associated with medicinal plant Arctium lappa L. and their potential for host plant growth promoting.

Arctium lappa L. is one of the medicinal and food homologous plants in China, which is rich in nutrients and medicinal ingredients. The use of plant growth-promoting (PGP) endophytic bacteria is an alternative to reducing chemical fertilizers in agricultural production. The aim of this study was to analyze the diversity of endophytic bacteria in different cultivars of A. lappa L. collected from two geographical locations in China and evaluate PGP traits of the isolates and their potential PGP ability in greenhouse condition. Endophytic bacterial community was investigated by culture-dependent and culture-independent methods. Isolates were screened and investigated for multiple PGP traits, and representative strains were inoculated host seedlings to evaluate the growth promoting effect. A total of 348 endophytic bacteria were obtained and they were distributed into 4 phyla and 30 genera. In addition, high throughput sequencing revealed more abundant bacterial community, including 17 bacterial phyla and 207 genera. A high proportion of PGP traits were detected, including production of indole acetic acid, siderophore, ammonia and phosphate solubilization. Four representative strains with multiple PGP traits of the most dominant genera (Bacillus, Pantoea, Microbacterium and Pseudomonas) were further selected for host inoculation and growth promoting evaluation, and they significantly increase seedlings length, root length and fresh weight. This study demonstrated that A. lappa L. harbors abundant endophytic bacteria, and some endophytic bacteria showed good potential for the development of microbial fertilizer in the future.

Microglia-derived PDGFB promotes neuronal potassium currents to suppress basal sympathetic tonicity and limit hypertension.

Although many studies have addressed the regulatory circuits affecting neuronal activities, local non-synaptic mechanisms that determine neuronal excitability remain unclear. Here, we found that microglia prevented overactivation of pre-sympathetic neurons in the hypothalamic paraventricular nucleus (PVN) at steady state. Microglia constitutively released platelet-derived growth factor (PDGF) B, which signaled via PDGFRα on neuronal cells and promoted their expression of Kv4.3, a key subunit that conducts potassium currents. Ablation of microglia, conditional deletion of microglial PDGFB, or suppression of neuronal PDGFRα expression in the PVN elevated the excitability of pre-sympathetic neurons and sympathetic outflow, resulting in a profound autonomic dysfunction. Disruption of the PDGFBMG-Kv4.3Neuron pathway predisposed mice to develop hypertension, whereas central supplementation of exogenous PDGFB suppressed pressor response when mice were under hypertensive insult. Our results point to a non-immune action of resident microglia in maintaining the balance of sympathetic outflow, which is important in preventing cardiovascular diseases.

Safety and Effectiveness of Inhaling Different Dosage Recombinant Human Interferon α1B for Bronchiolitis in Children: a Systematic Review and Meta-Analysis.

Purpose: To systematically evaluate the safety and effectiveness of different dosages of recombinant human interferon α1b (IFNα1b) inhaled for bronchiolitis in children. Methods: 7 databases, including PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang Database, and VIP, were searched. The search time was from their inception dates to March 28, 2022. A randomized controlled trial (RCT) of 2 µg/kg IFNα1b (low dosage group) monotherapy or in combination with other drugs vs. 4 µg/kg IFNα1b (high dosage group) monotherapy or in combination with the other drugs was included. The risk of bias 2.0 evaluated the RCT's quality, and the grading of recommendations assessment, development and evaluation (GRADE) tool was used for evaluating the overall quality of the evidence. Then, a meta-analysis was performed by RevMan 5.4. Results: A total of 13 RCTs with 1719 children were included. The meta-analysis results showed that the high dosage group was significantly shorter than the low dosage group of the duration of hospital stays (MD = -0.40, 95%CI (-0.73, -0.07), P = 0.02) (low quality), three depressions sign disappearing time (MD = -0.60, 95%CI (-1.05, -0.14), P = 0.010) (low quality), and wheeze disappearing time (MD = -0.62, 95%CI (-1.17, -0.06), = 0.03) (low quality). There was no significant difference between the two groups in coughing disappearing time, pulmonary rales disappearing time, wheezing sound disappearing time, or adverse event rates. Conclusions: Compared with low dosage IFNα1b, high dosage IFNα1b reduces the duration of hospital stays, the disappearance time of the three depression signs, and the disappearance time of wheeze in the treatment of bronchiolitis in children. Limited by the low quality of the evidence, the conclusions still need to be supported by high-quality studies.

Dietary Fat and Polyunsaturated Fatty Acid Intakes during Childhood Are Prospectively Associated with Puberty Timing Independent of Dietary Protein.

Dietary fat and fat quality have been inconsistently associated with puberty timing. The aim of this study was to investigate the prospective associations of dietary fat, saturated fatty acid (SFA), polyunsaturated fatty acid (PUFA), and monounsaturated fatty acid (MUFA) with puberty timing. Using longitudinal data from China Health and Nutrition Survey (CHNS) and Southwest China Childhood Nutrition and Growth (SCCNG) Study, we analyzed dietary data, anthropometric measurements, and potential confounders. Dietary intakes were assessed by 3-day 24-h recalls. Age at Tanner stage 2 for breast/genital development (B2/G2) and age at menarche/voice break (M/VB) were used as puberty development markers. Cox proportional hazard regression models were used to estimate the relevance of dietary intake of total fat, SFA, PUFA, and MUFA on puberty timing. Among 3425 girls and 2495 boys, children with higher intakes of total fat and PUFA were more likely to reach their B2/G2 or M/VB at an earlier age. Associations were not attenuated on additional adjustment for childhood dietary protein intake. However, higher intakes of SFA or MUFA were not independently associated with puberty development. A higher intake of dietary fat and PUFA in prepuberty was associated with earlier puberty timing, which was independent of dietary protein intake.

Deleterious Genetic Variation Across the NOD Signaling Pathway Is Associated With Reduced NFKB Signaling Transcription and Upregulation of Alternative Inflammatory Transcripts in Pediatric Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease may arise with inadequate immune response to intestinal bacteria. NOD2 is an established gene in Crohn's disease pathogenesis, with deleterious variation associated with reduced NFKB signaling. We hypothesized that deleterious variation across the NOD2 signaling pathway impacts on transcription. METHODS: Treatment-naïve pediatric inflammatory bowel disease patients had ileal biopsies for targeted autoimmune RNA-sequencing and blood for whole exome sequencing collected at diagnostic endoscopy. Utilizing GenePy, a per-individual, per-gene score, genes within the NOD signaling pathway were assigned a quantitative score representing total variant burden. Where multiple genes formed complexes, GenePy scores were summed to create a "complex" score. Normalized transcript expression of 95 genes within this pathway was retrieved. Regression analysis was performed to determine the impact of genomic variation on gene transcription. RESULTS: Thirty-nine patients were included. Limited clustering of patients based on NOD signaling transcripts was related to underlying genomic variation. Patients harboring deleterious variation in NOD2 had reduced NOD2 (ß = -0.702, P = 4.3 × 10-5) and increased NFKBIA (ß = 0.486, P = .001), reflecting reduced NFKB signal activation. Deleterious variation in the NOD2-RIPK2 complex was associated with increased NLRP3 (ß = 0.8, P = 3.1475 × 10-8) and TXN (ß = -0.417, P = 8.4 × 10-5) transcription, components of the NLRP3 inflammasome. Deleterious variation in the TAK1-TAB complex resulted in reduced MAPK14 transcription (ß = -0.677, P = 1.7 × 10-5), a key signal transduction protein in the NOD2 signaling cascade and increased IFNA1 (ß = 0.479, P = .001), indicating reduced transcription of NFKB activators and alternative interferon transcription in these patients. CONCLUSIONS: Data integration identified perturbation of NOD2 signaling transcription correlated with genomic variation. A hypoimmune NFKB signaling transcription response was observed. Alternative inflammatory pathways were activated and may represent therapeutic targets in specific patients.

Implementing a Tailored Psychosocial Distress Screening Protocol in a Head and Neck Cancer Program.

OBJECTIVES/HYPOTHESIS: Psychosocial distress is common among patients with head and neck cancer (HNC) and is associated with poorer quality of life and clinical outcomes. Despite these risks, distress screening is not widely implemented in HNC care. In this study, we investigated the prevalence of psychosocial distress and its related factors in routine care of patients with HNC. METHODS: Data from medical records between September 2017 and March 2020 were analyzed. Psychosocial distress was measured by the National Comprehensive Cancer Network's Distress Thermometer (DT), and a modified HNC-specific problem list; depression and anxiety were assessed using the Patient Health Questionnaire-4. Descriptive statistics and logistic regression were conducted to report prevalence of distress, depression and anxiety, and factors associated with clinical distress. Implementation outcomes, including rates of referrals and follow-up for distressed patients, are also reported. RESULTS: Two hundred and eighty seven HNC patients completed the questionnaire (age 64.3 ± 14.9 years), with a mean distress score of 4.51 ± 3.35. Of those, 57% (n = 163) reported clinical distress (DT ≥ 4). Pain (odds ratio [OR] = 3.31, 95% CI = 1.75-6.26), fatigue (OR = 2.43, 95% CI = 1.1.7-5.05), anxiety (OR = 1.63, 95% CI = 1.30-2.05), and depression (OR = 1.51, 95% CI = 1.04-2.18) were significantly associated with clinical distress (P < .05). Of patients identified as distressed, 79% received same-day psychosocial evaluation. CONCLUSIONS: Clinical distress was identified in 57% of patients who completed the questionnaire, suggesting that an ultra-brief psychosocial screening protocol can be implemented in routine ambulatory oncology care, and identifies patients whose distress might otherwise go unrecognized. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1600-1608, 2022.

Effects of acupuncture on cartilage p38MAPK and mitochondrial pathways in animal model of knee osteoarthritis: A systematic evaluation and meta-analysis.

Background: Most previous studies on acupuncture in the treatment of knee osteoarthritis (KOA) have focused on improving functional efficacy and safety, while related mechanisms have not been systematically reviewed. Acupuncture modulates cytokines to attenuate cartilage extracellular matrix degradation and apoptosis, key to the pathogenesis of KOA, but the mechanisms are complex. Objectives: The purpose of this study is to assess the efficacy of acupuncture quantitatively and summarily in animal studies of KOA. Methods: Nine databases including PubMed, Embase, Web of Science (including Medline), Cochrane library, Scopus, CNKI, Wan Fang, and VIP were searched to retrieve animal studies on acupuncture interventions in KOA published since the inception of the journal. Relevant literature was screened, and information extracted. Meta-analysis was performed using Revman 5.4 and Stata 17.0 software. Results: The 35 included studies involved 247 animals, half of which were in acupuncture groups and half in model groups. The mean quality level was 6.7, indicating moderate quality. Meta-analysis showed that acupuncture had the following significant effects on cytokine levels in p38MAPK and mitochondrial pathways: (1) p38MAPK pathway: It significantly inhibits p38MAPK, interleukin-1beta (IL-1ß), tumor necrosis factor alpha (TNF-α), phosphorylated (p)-p38MAPK, matrix metalloproteinase-13 (MMP-13), MMP-1, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMST-5) expression, and significantly increased the expression of collagen II and aggrecan. (2) mitochondrial pathway: It significantly inhibited the expression of Bcl-2-associated X protein (Bax), cysteine protease-3 (caspase-3), caspase-9, and Cytochrome-c (Cyt-c). And significantly increased the expression of B cell lymphocytoma-2 (Bcl-2). In addition, acupuncture significantly reduced chondrocyte apoptosis, Mankin's score (a measure of cartilage damage), and improved cartilage morphometric characteristics. Conclusion: Acupuncture may inhibit cytokine expression in the p38MAPK pathway to attenuate cartilage extracellular matrix degradation, regulate cytokines in the mitochondrial pathway to inhibit chondrocyte apoptosis, and improve cartilage tissue-related phenotypes to delay cartilage degeneration. These findings provide possible explanations for the therapeutic mechanisms and clinical benefits of acupuncture for KOA. Systematic review registration: https://inplasy.com, identifier INPLASY20 2290125.

Role of dietary factors in the prevention and treatment for depression: an umbrella review of meta-analyses of prospective studies.

The role of diet in depression is becoming increasingly acknowledged. This umbrella review aimed to summarize comprehensively the current evidence reporting the effects of dietary factors on the prevention and treatment of depression. PubMed, Embase, and the Cochrane Library were searched up to June 2021 to identify relevant meta-analyses of prospective studies. Twenty-eight meta-analyses, with 40 summary estimates on dietary patterns (n = 8), food and beverages (n = 19), and nutrients (n = 13) were eligible. The methodological quality of most meta-analyses was low (50.0%) or very low (25.0%). Quality of evidence was moderate for inverse associations for depression incidence with healthy diet [risk ratio (RR): 0.74, 95% confidential interval (CI), 0.48-0.99, I2 = 89.8%], fish (RR: 0.88, 95% CI, 0.79-0.97, I2 = 0.0%), coffee (RR: 0.89, 95% CI, 0.84-0.94, I2 = 32.9%), dietary zinc (RR: 0.66, 95% CI 0.50-0.82, I2 = 13.9%), light to moderate alcohol (<40 g/day, RR: 0.77, 95% CI, 0.74-0.83, I2 = 20.5%), as well as for positive association with sugar-sweetened beverages (RR: 1.05, 95% CI, 1.01-1.09, I2 = 0.0%). For depression treatment, moderate-quality evidence was identified for the effects of probiotic [standardized mean difference (SMD): -0.31, 95% CI, -0.56 to -0.07, I2 = 48.2%], omega-3 polyunsaturated fatty acid (SMD: -0.28, 95% CI, -0.47 to -0.09, I2 = 75.0%) and acetyl-L-carnitine (SMD: -1.10, 95% CI, -1.65 to -0.56, I2 = 86.0%) supplementations. Overall, the associations between dietary factors and depression had been extensively evaluated, but none of them were rated as high quality of evidence, suggesting further studies are likely to change the summary estimates. Thus, more well-designed research investigating more detailed dietary factors in association with depression is warranted.

Intragenic heterochromatin-mediated alternative polyadenylation modulates miRNA and pollen development in rice.

Despite a much higher proportion of intragenic heterochromatin-containing genes in crop genomes, the importance of intragenic heterochromatin in crop development remains unclear. Intragenic heterochromatin can be recognised by a protein complex, ASI1-AIPP1-EDM2 (AAE) complex, to regulate alternative polyadenylation. Here, we investigated the impact of rice ASI1 on global poly(A) site usage through poly(A) sequencing and ASI1-dependent regulation on rice development. We found that OsASI1 is essential for rice pollen development and flowering. OsASI1 dysfunction has an important impact on global poly(A) site usage, which is closely related to heterochromatin marks. Intriguingly, OsASI1 interacts with the intronic heterochromatin of OsXRNL, a nuclear XRN family exonuclease gene involved in the processing of an miRNA precursor, to promote the processing of full-length OsXRNL and regulate miRNA abundance. We found that OsASI1-mediated regulation of pollen development partially depends on OsXRNL. Finally, we characterised the rice AAE complex and its involvement in alternative polyadenylation and pollen development. Our findings help to elucidate an epigenetic mechanism governing miRNA abundance and rice development, and provide a valuable resource for studying the epigenetic mechanisms of many important processes in crops.