Effect of multicomponent intervention on malnutrition in older adults: A multicenter randomized clinical trial.

BACKGROUND & AIMS: Malnutrition is a significant geriatric syndrome (GS) prevalent in older adults and seriously affects patient prognosis and quality of life. We assessed the impact of the multicomponent intervention of health education, dietary advice, and exercise with oral nutritional supplementation (ONS) on nutritional status, body composition, physical functions, and quality of life. METHODS: This multicenter randomized clinical trial (RCT) was performed from April 2021 to April 2022. The intervention lasted for 12 weeks, and 99 older adults with malnutrition or at risk of malnutrition were enrolled in six nursing homes. All participants were randomly assigned to the control (health education plus standard diet plus exercise) or research (health education plus standard diet plus exercise plus ONS) group. The research group consumed ONS (244 kcal, 9.8g protein, and 9.6g fat per time) twice a day between meals. The primary outcomes were changes in the nutritional status and body composition from baseline to 12 weeks. The secondary outcomes were changes in physical function, quality of life and nutritional associated other blood markers. RESULTS: For primary outcomes, after 12 weeks, body weight increased similarly in both treatment arms (time × treatment effect, P > 0.05). There were no between-group differences in body mass index (BMI) or mini nutritional assessment tool-short form (MNA-SF) scores (time × treatment effects, P > 0.05). The MNA-SF score from 11.0 (10.5, 12.0) to 13.0 (11.0, 13.0) in the research group and from 11.0 (10.0, 12.0) to 12.0 (11.0, 13.0) in the control group (both P < 0.05). There were no between-group differences in the skeletal muscle mass index (SMI), fat-free mass index (FFMI), appendicular skeletal muscle mass (ASMM), fat mass (FAT), or leg muscle mass (LMM) (time × treatment effects, P > 0.05). Both groups showed similar and highly significant increases in SMI, FFMI, and LMM after (P < 0.05). The research group showed an increase in fat-free mass (FFM) and ASMM and a decrease in the percent of body fat (PBF) and waist circumference (WC) (P < 0.05). For secondary outcomes, There were no between-group differences in grip strength, short physical performance battery (SPPB), 6-min walking distance (6MWD), activities of daily living (ADL), instrumental activities of daily living (IADL), frailty status (FRAIL), mini-mental state examination (MMSE), Tinetti, geriatric depression scale-15 (GDS-15), or 12-item short form survey (SF-12) (time × treatment effects, P > 0.05). Although there was no significant difference, the 6MWD changed differentially between the two treatment arms during the study period in favor of the research group. Although not significant, SF-12 scores improved after 12 weeks in both groups. No between-group differences were observed in prealbumin (PRE), c-reactive protein (CRP), vitamin D (VIT-D), insulin-like growth factor 1 (IGF-1), alanine transaminase (ALT), aspartate aminotransferase (AST), serum creatinine (Scr), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), insulin, and adiponectin levels (time × treatment effects, P > 0.05). Insulin and adiponectin levels were significantly higher in the control group (P < 0.05). CONCLUSION: The twelve-week multicomponent intervention improved the nutritional status of older people in China at risk of malnutrition. ONS may enhance the effects of exercise on muscle mass. This clinical trial was registered (https://www. CLINICALTRIALS: gov). The trial number is ChiCTR2000040343.

Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses.

BACKGROUND: Ginkgo biloba L. preparations (GBLPs) are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke (IS). Recently, several systematic reviews (SRs) and meta-analyses (MAs) of GBLPs for IS have been published. OBJECTIVE: This overview aims to assess the quality of related SRs and MAs. SEARCH STRATEGY: PubMed, Embase, Cochrane Library, Web of Science, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Journals databases were searched from their inception to December 31, 2022. INCLUSION CRITERIA: SRs and MAs of randomized controlled trials (RCTs) that explored the efficacy of GBLPs for patients with IS were included. DATA EXTRACTION AND ANALYSIS: Two independent reviewers extracted data and assessed the methodological quality, risk of bias (ROB), reporting quality, and credibility of evidence of the included SRs and MAs using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Additionally, descriptive analysis and data synthesis were conducted. RESULTS: Twenty-nine SRs/MAs involving 119 outcomes were included in this review. The overall methodological quality of all SRs/MAs was critically low based on AMSTAR 2, and 28 had a high ROB based on the ROBIS. According to the PRISMA statement, the reporting items of the included SRs/MAs are relatively complete. The results based on GRADE showed that of the 119 outcomes, 8 were rated as moderate quality, 24 as low quality, and 87 as very low quality. Based on the data synthesis, GBLPs used in conjunction with conventional treatment were superior to conventional treatment alone for decreasing neurological function scores. CONCLUSION: GBLPs can be considered a beneficial supplemental therapy for IS. However, because of the low quality of the existing evidence, high-quality RCTs and SRs/MAs are warranted to further evaluate the benefits of GBLPs for treating IS. Please cite this article as: Meng TT, You YP, Li M, Guo JB, Song XB, Ding JY, Xie XL, Li AQ, Li SJ, Yin XJ, Wang P, Wang Z, Wang BL, He QY. Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses. J Integr Med. 2024;22(2): 163-179.

Recent advances in the potential effects of natural products from traditional Chinese medicine against respiratory diseases targeting ferroptosis.

Respiratory diseases, marked by structural changes in the airways and lung tissues, can lead to reduced respiratory function and, in severe cases, respiratory failure. The side effects of current treatments, such as hormone therapy, drugs, and radiotherapy, highlight the need for new therapeutic strategies. Traditional Chinese Medicine (TCM) offers a promising alternative, leveraging its ability to target multiple pathways and mechanisms. Active compounds from Chinese herbs and other natural sources exhibit anti-inflammatory, antioxidant, antitumor, and immunomodulatory effects, making them valuable in preventing and treating respiratory conditions. Ferroptosis, a unique form of programmed cell death (PCD) distinct from apoptosis, necrosis, and others, has emerged as a key area of interest. However, comprehensive reviews on how natural products influence ferroptosis in respiratory diseases are lacking. This review will explore the therapeutic potential and mechanisms of natural products from TCM in modulating ferroptosis for respiratory diseases like acute lung injury (ALI), asthma, pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD), lung ischemia-reperfusion injury (LIRI), pulmonary hypertension (PH), and lung cancer, aiming to provide new insights for research and clinical application in TCM for respiratory health.

Folic acid supplementation prevents high body fat-induced bone loss through TGR5 signaling pathways.

Osteoporosis caused by bone loss is one of the serious global public health problems. Folic acid is a B vitamin with multiple physiological functions such as lipid regulation and antioxidant capacity, and its potential to improve bone loss has attracted our attention. Through NHANES database analysis, we found that folic acid intake was significantly correlated with whole-body bone mineral density (BMD) in people aged 20-60 years, and the association may be mediated by the body fat rate. Male C57Bl/6 mice were fed either a normal diet or a high-fat diet, and folic acid was added to drinking water for supplementation. Our results indicated that mice with high body fat showed bone microstructure damage and bone loss, while folic acid supplementation improved bone quality. At the same time, we found that mice with high body fat exhibited abnormal blood lipids, dysregulation of intestinal flora, and metabolic disorders. Folic acid supplementation improved these phenomena. Through the network analysis of intestinal flora and metabolites, we found that LCA and TGR5 may play important roles. The results showed that folic acid promoted the expression of LCA and TGR5 in mice, increased the phosphorylation of AMPK, and decreased the phosphorylation of NF-κB and ERK, thereby reducing bone loss. In summary, folic acid intake is closely related to BMD, and folic acid supplementation can prevent high body fat-induced bone loss. Our study provides new ideas and an experimental basis for preventing bone loss and osteoporosis.

Acupuncture Versus Biofeedback for Treatment of Functional Anorectal Pain.

BACKGROUND/AIMS: Functional anorectal pain is one of several types of functional anorectal disorders. In this study, we compared the effectiveness of acupuncture (intervention) and biofeedback (control) as treatment for patients with functional anorectal pain. MATERIALS AND METHODS: This prospective, single-center, randomized, and comparative study examined 68 patients with functional anorectal pain who were recruited from June 2017 to January 2019 at the Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Patients were randomly assigned to receive acupuncture or biofeedback. Patients in the acupuncture group received acupuncture at Zhongliao (BL33), Xialiao (BL34), Ganshu (BL18), Shenshu (BL23), and Dachangshu (BL25). Patients in the biofeedback group received pelvic floor biofeedback therapy, consisting of Kegel pelvic floor muscle training and electrical stimulation. Patients in both groups received 20 treatments over 4 weeks. The primary outcome was pain score on a visual analog scale, and the secondary outcomes were results from the MOS 36-item short-form health survey (SF-36) quality of life questionnaire, the self-rating depression scale, and the self-rating anxiety scale. RESULTS: Visual analog scale pain scores significantly decreased in both of the groups with treatment (both P < .01). The final visual analog scale score was significantly lower in patients with pelvic floor dyssynergia who were treated with biofeedback (1.40 ± 0.97 vs. 5.30 ± 1.70) (P < .05). The 2 groups had similar decreases in self-rating depression scale and self-rating anxiety scale scores. Intriguingly, the acupuncture group had better mental health outcomes (P <.05). CONCLUSION: Both acupuncture and biofeedback therapy reduced the pain of patients with functional anorectal pain. Biofeedback provided more relief in patients with pelvic floor dyssynergia, and acupuncture provided greater improvements in mental health status.

Clinical application of real-time continuous glucose monitoring system during postoperative enteral nutrition therapy in esophageal cancer patients.

BACKGROUND: Enteral nutrition (EN) support therapy increases the risk of abnormal blood glucose (BG). The aim of this study is to evaluate the clinical value of a real-time continuous glucose monitoring (rt-CGM) system in BG monitoring during postoperative EN support therapy in patients with esophageal cancer. METHODS: Patients without diabetes mellitus (DM) with esophageal cancer who planned to receive postoperative EN were enrolled. With the self-monitoring of BG value as the reference BG, the accuracy of rt-CGM was evaluated by the mean absolute relative difference (MARD) value, correlation efficient, agreement analysis, and Parkes and Clarke error grid plot. Finally, paired t tests were used to compare the differences in glucose fluctuations between EN and non-EN days and slow and fast days. RESULTS: The total MARD value of the rt-CGM system was 13.53%. There was a high correlation between interstitial glucose and fingertip capillary BG (consistency correlation efficient = 0.884 [95% confidence interval, 0.874-0.894]). Results of 15/15%, 20/20%, 30/30% agreement analysis were 58.51%, 84.71%, and 99.65%, respectively. The Parkes and Clarke error grid showed that the proportion of the A and B regions were 100% and 99.94%, respectively. The glucose fluctuations on EN days vs non-EN days and on fast days vs slow days were large, and the difference was statistically significant (P < 0.001). CONCLUSION: The rt-CGM system achieved clinical accuracy and can be used as a new option for glucose monitoring during postoperative EN therapy. The magnitude of glucose fluctuation during EN therapy remains large, even in the postoperative population without DM.

Schisandrin B from Schisandra chinensis alleviated pain via glycine receptors, Nav1.7 channels and Cav2.2 channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis, the dried and ripe fruit of the magnolia family plant Schisandra chinensis (Turcz.) Baill, was commonly used in traditional analgesic prescription. Studies have shown that the extract of Schisandra chinensis (SC) displayed analgesic activity. However, the analgesic active component and the exact mechanisms have yet to be revealed. AIM OF THE STUDY: The present study was to investigate the anti-nociceptive constituent of Schisandra chinensis, assess its analgesic effect, and explore the potential molecular mechanisms. MATERIALS AND METHODS: The effects of a series of well-recognized compounds from SC on glycine receptors were investigated. The analgesic effect of the identified compound was evaluated in three pain models. Mechanistic studies were performed using patch clamp technique on various targets expressed in recombinant cells. These targets included glycine receptors, Nav1.7 sodium channels, Cav2.2 calcium channels et al. Meanwhile, primary cultured spinal dorsal horn (SDH) neurons and dorsal root ganglion (DRG) neurons were also utilized. RESULTS: Schisandrin B (SchB) was a positive allosteric modulator of glycine receptors in spinal dorsal horn neurons. The EC50 of SchB on glycine receptors in spinal dorsal horn neurons was 2.94 ± 0.28 µM. In three pain models, the analgesic effect of SchB was comparable to that of indomethacin at the same dose. Besides, SchB rescued PGE2-induced suppression of α3 GlyR activity and alleviated persistent pain. Notably, SchB could also potently decrease the frequency of action potentials and inhibit sodium and calcium channels in DRG neurons. Consistent with the data from DRG neurons, SchB was also found to significantly block Nav1.7 sodium channels and Cav2.2 channels in recombinant cells. CONCLUSION: Our results demonstrated that, Schisandrin B, the primary lignan component of Schisandra chinensis, may exert its analgesic effect by acting on multiple ion channels, including glycine receptors, Nav1.7 channels, and Cav2.2 channels.

Efficacy and mechanism of acupuncture in animal models of depressive-like behaviors: a systematic review and meta-analysis.

Background: Many studies have investigated the efficacy of acupuncture in treating depression, but the mechanism of acupuncture for depression is still controversial and there is a lack of meta-analysis of mechanisms. Consequently, we investigated acupuncture's efficacy and mechanism of depression. Methods: We searched the Cochrane Library, PubMed, EMBASE, Web of Science. The SYRCLE Risk of Bias Tool was used to assess bias risk. Meta-analysis was performed using Stata 15.0 for indicators of depression mechanisms, body weight and behavioral tests. Results: A total of 22 studies with 497 animals with depressive-like behaviors were included. Meta-analysis showed that acupuncture significantly increased BDNF [SMD = 2.40, 95% CI (1.33, 3.46); I2 = 86.6%], 5-HT [SMD = 2.28, 95% CI (1.08, 3.47); I2 = 87.7%] compared to the control group (p < 0.05), and significantly reduced IL-1ß [SMD = -2.33, 95% CI (-3.43, -1.23); I2 = 69.6%], CORT [SMD = -2.81, 95% CI (-4.74, -0.87); I2 = 86.8%] (p < 0.05). Acupuncture improved body weight [SMD = 1.35, 95% CI (0.58, 2.11); I2 = 84.5%], forced swimming test [SMD = -1.89, 95% CI (-2.55, -1.24); I2 = 76.3%], open field test (crossing number [SMD = 3.08, 95% CI (1.98, 4.17); I2 = 86.7%], rearing number [SMD = 2.53, 95% CI (1.49, 3.57); I2 = 87.0%]) (p < 0.05) compared to the control group. Conclusion: Acupuncture may treat animals of depressive-like behaviors by regulating neurotrophic factors, neurotransmitters, inflammatory cytokines, neuroendocrine system. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023403318, identifier (CRD42023403318).

Edgeworthia gardneri (Wall.) Meisn. Ethanolic Extract Attenuates Endothelial Activation and Alleviates Cardiac Ischemia-Reperfusion Injury.

Endothelial pro-inflammatory activation is pivotal in cardiac ischemia-reperfusion (I/R) injury pathophysiology. The dried flower bud of Edgeworthia gardneri (Wall.) Meisn. (EG) is a commonly utilized traditional Tibetan medicine. However, its role in regulating endothelium activation and cardiac I/R injury has not been investigated. Herein, we showed that the administration of EG ethanolic extract exhibited a potent therapeutic efficacy in ameliorating cardiac endothelial inflammation (p < 0.05) and thereby protecting against myocardial I/R injury in rats (p < 0.001). In line with the in vivo findings, the EG extract suppressed endothelial pro-inflammatory activation in vitro by downregulating the expression of pro-inflammatory mediators (p < 0.05) and diminishing monocytes' firm adhesion to endothelial cells (ECs) (p < 0.01). Mechanistically, we showed that EG extract inhibited the nuclear factor kappa-B (NF-κB), c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase (ERK), and p38 mitogen-activated protein kinase (MAPK) signaling pathways to attenuate EC-mediated inflammation (p < 0.05). Collectively, for the first time, this study demonstrated the therapeutic potential of EG ethanolic extract in alleviating I/R-induced inflammation and the resulting cardiac injury through its inhibitory role in regulating endothelium activation.

Efficacy and immune-inflammatory mechanism of acupuncture-related therapy in animal models of knee osteoarthritis: a preclinical systematic review and network meta-analysis.

BACKGROUND: Many KOA patients have not reached indications for surgery, thus we need to find effective non-surgical treatments. Acupuncture is thought to have the potential to modulate inflammation and cytokines in KOA through the immune system. However, the mechanisms have not been elucidated, and there is no network Meta-analysis of acupuncture on KOA animals. So we evaluate the effect and mechanism of acupuncture-related therapy in KOA animals. METHODS: A comprehensive search was conducted in multiple databases including PubMed, Web of Science, Embase, CBM, CNKI, WanFang, and VIP Database to identify relevant animal studies focusing on acupuncture therapy for KOA. The included studies were assessed for risk of bias using SYRCLE's Risk of Bias tool. Subsequently, pair-wise meta-analysis and network meta-analysis were performed using Stata 15.0 software, evaluating outcomes such as Lequesne index scale, Mankin score, IL-1ß, TNF-α, MMP3, and MMP13. RESULTS: 56 RCTs with 2394 animals were included. Meta-analysis showed that among the 6 outcomes, there were significant differences between acupuncture and model group; the overall results of network meta-analysis showed that the normal group or sham operation group performed the best, followed by the acupotomy, acupuncture, and medicine group, and the model group had the worst effect, and there were significant differences between 6 interventions. CONCLUSIONS: Acupuncture-related therapy can be a possible treatment for KOA. The mechanism involves many immune-inflammatory pathways, which may be mediated by DAMPs/TLR/NF-κB/MAPK,PI3K/Akt/NF-κB pathway, or IFN-γ/JAK-STAT pathway. It needs to be further confirmed by more high-quality animal experiments or meta-analysis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO identifier: CRD42023377228.

Ganoderic acids alleviate atherosclerosis by inhibiting macrophage M1 polarization via TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND AND AIMS: Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid infiltration and plaque formation in blood vessel walls. Ganoderic acids (GA), a class of major bioactive compounds isolated from the Chinese traditional medicine Ganoderma lucidum, have multiple pharmacological activities. This study aimed to determine the anti-atherosclerotic effect of GA and reveal the pharmacological mechanism. METHODS: ApoE-/- mice were fed a high-cholesterol diet and treated with GA for 16 weeks to induce AS and identify the effect of GA. Network pharmacological analysis was performed to predict the anti-atherosclerotic mechanisms. An invitro cell model was used to explore the effect of GA on macrophage polarization and the possible mechanism involved in bone marrow dereived macrophages (BMDMs) and RAW264.7 cells stimulated with lipopolysaccharide or oxidized low-density lipoprotein. RESULTS: It was found that GA at 5 and 25 mg/kg/d significantly inhibited the development of AS and increased plaque stability, as evidenced by decreased plaque in the aorta, reduced necrotic core size and increased collagen/lipid ratio in lesions. GA reduced the proportion of M1 macrophages in plaques, but had no effect on M2 macrophages. In vitro experiments showed that GA (1, 5, 25 µg/mL) significantly decreased the proportion of CD86+ macrophages and the mRNA levels of IL-6, IL-1ß, and MCP-1 in macrophages. Experimental results showed that GA inhibited M1 macrophage polarization by regulating TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS: This study demonstrated that GA play an important role in plaque stability and macrophage polarization. GA exert the anti-atherosclerotic effect partly by regulating TLR4/MyD88/NF-κB signaling pathways to inhibit M1 polarization of macrophages. Our study provides theoretical basis and experimental data for the pharmacological activity and mechanisms of GA against AS.

Enhancing the Development and Growth of Infant Cerebral Palsy Rats Using Selective Spinal Manipulations.

Cerebral palsy (CP) is a refractory pediatric disease with a high prevalence, high disability rate, and difficult treatment. A variety of treatments are currently used for CP. The treatment involves drug and non-drug therapy. Traditional Chinese medicine external therapy is a very distinctive treatment method in non-drug therapy. As one of the external therapies of traditional Chinese medicine, massage is used in treating cerebral palsy and has good efficacy, small side effects, and strong operability. As a part of TCM external therapy, selective spinal manipulation can effectively promote the growth and development of infant rats with cerebral palsy.The operation was mainly divided into four steps: first, the rubbing method was applied to the spine and both sides of the spine for 1 min. The pressing and kneading method was applied to the spine for 5 min, and the muscles on both sides of the spine for 5 min. Second, pressing and kneading the sensitive local acupoints in the spine for 2 min were performed. Thirdly, the affected limb was treated by twisting method for 1 min. Fourth, the rubbing method was applied to a midline from the forehead to the back of the brain for 1 min. This study aimed to use selective spinal manipulation to treat infant rats with cerebral palsy. The weight, Rotarod test, Foot-fault score, and growth hormone of infant rats with cerebral palsy were detected to understand the effect of selective spinal manipulation on the growth and development of infant rats with cerebral palsy. The results showed that it can promote weight gain, improve balance ability and motor function, promote growth and development of infant cerebral palsy rats, promote growth hormone secretion, and increase the temperature of sensitive parts of the back.

Cortical depth profiles in primary visual cortex for illusory and imaginary experiences.

Visual illusions and mental imagery are non-physical sensory experiences that involve cortical feedback processing in the primary visual cortex. Using laminar functional magnetic resonance imaging (fMRI) in two studies, we investigate if information about these internal experiences is visible in the activation patterns of different layers of primary visual cortex (V1). We find that imagery content is decodable mainly from deep layers of V1, whereas seemingly 'real' illusory content is decodable mainly from superficial layers. Furthermore, illusory content shares information with perceptual content, whilst imagery content does not generalise to illusory or perceptual information. Together, our results suggest that illusions and imagery, which differ immensely in their subjective experiences, also involve partially distinct early visual microcircuits. However, overlapping microcircuit recruitment might emerge based on the nuanced nature of subjective conscious experience.

Selenium in the treatment of mild-to-moderate Graves' orbitopathy: a 5-year prospective controlled cohort study.

PURPOSE: Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease. However, limited studies have investigated the actual efficacy of selenium in GO therapy. This longitudinal study explored the effect of selenium on QOL and prognosis of patients with mild-to-moderate GO. METHODS: We conducted a 5-year prospective controlled cohort clinical trial to determine the effect of selenium on 74 patients with mild-to-moderate GO. Patients received selenium yeast or placebo orally for 6 months and were followed up at 6 months and at 5 years by biochemical examination, ophthalmologist evaluation and QOL questionnaire to assess oculopathy and QOL. RESULTS: (1) During a follow-up period of 3-6 months, in the selenium group, the symptoms of tearing, grittiness and conjunctival congestion improved (P < 0.01); clinical activity scores and total GO-QOL scores increased relative to baseline (P < 0.01); TRAb was decreased at the 6-month evaluation (P = 0.003); and patients treated with selenium had a higher rate of improvement and a lower rate of worsening than patients treated with placebo (P < 0.05). (2) Exploratory evaluations at 6 months after drug withdrawal confirmed the earlier results; further changes included alleviation of blurred vision and double vision symptoms in the selenium group (P < 0.01). (3) At the 5-year follow-up, compared with baseline, proptosis, clinical activity scores, TRAb level and total GO-QOL scores in both the selenium and placebo groups were significantly improved (P < 0.01). CONCLUSION: Six months of selenium supplementation may effectively change the early course of mild-to-moderate GO, but this regimen makes no difference in long-term outcomes.

Diatom-dinoflagellate succession in the Bohai Sea: The role of N/P ratios and dissolved organic nitrogen components.

Dissolved organic nitrogen (DON) is a pivotal component of total dissolved nitrogen pools, serving as a crucial nitrogen source for phytoplankton. This study investigated the impact of nitrogen-to-phosphorus (N/P) ratios and different DON components (hydrophilic vs hydrophobic DON) on diatom-dinoflagellate succession through field culture experiments. Results showed that dinoflagellates have a competitive advantage under high N/P ratios and phosphorus limitation, regardless of DON or DIN treatments. Hydrophilic DON exhibits greater bioavailability than hydrophobic DON (40.6% vs. 21.7 %), resulting in increased algal biomass and diatoms dominance in the community. Additionally, DON was categorized into labile and refractory components (LDON and RDON) based on bioavailability. LDON primarily consists of protein-like components that can be readily consumed by algae, whereas RDON is primarily composed of humic-like components that are less accessible to algae. Diatoms and dinoflagellates exhibited differential responses to LDON and RDON, with diatoms thriving in high LDON environments, while dinoflagellates gained a competitive advantage when RDON was the predominant nitrogen source. Furthermore, a significant negative correlation was observed between bioavailable nitrogen concentration (BAN: DIN + LDON) and the ratio of dinoflagellates to diatoms (p<0.05). In conclusion, our study highlights the role of LDON in promoting diatom dominance, whereas environments dominated by RDON foster dinoflagellate success. These findings enhance our comprehension of diatom-dinoflagellate succession dynamics.

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.

Loureirin A Promotes Cell Differentiation and Suppresses Migration and Invasion of Melanoma Cells via WNT and AKT/mTOR Signaling Pathways.

Resina Draconis is a traditional Chinese medicine, with the in-depth research, its medicinal value in anti-tumor has been revealed. Loureirin A is extracted from Resina Draconis, however, research on the anti-tumor efficacy of Loureirin A is rare. Herein, we investigated the function of Loureirin A in melanoma. Our research demonstrated that Loureirin A inhibited the proliferation of and caused G0/G1 cell cycle arrest in melanoma cells in a concentration-dependent manner. Further study showed that the melanin content and tyrosinase activity was enhanced after Loureirin A treatment, demonstrated that Loureirin A promoted melanoma cell differentiation, which was accompanied with the reduce of WNT signaling pathway. Meanwhile, we found that Loureirin A suppressed the migration and invasion of melanoma cells through the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Taken together, this study demonstrated for the first time the anti-tumor effects of Loureirin A in melanoma cells, which provided a novel therapeutic strategy against melanoma.

Utilizing the photodynamic properties of curcumin to disrupt biofilms in Cutibacterium acnes: A promising approach for treating acne.

BACKGROUND: The treatment of acne vulgaris is often challenging due to the antibiotic resistance frequently observed in Cutibacterium acnes (C.acnes), a prevalent bacterium linked to this condition. OBJECTIVE: The objective of this research was to examine the impact of curcumin photodynamic therapy (PDT) on the survival of C.acnes and activity of biofilms produced by this microorganism. METHODS: Following the Clinical and Laboratory Standards Institute (CLSI) guidelines, we assessed the drug sensitivity of 25 clinical C.acnes strains to five antibiotics (erythromycin, clindamycin, tetracycline, doxycycline, minocycline) and curcumin by implementing the broth microdilution technique. In addition, we established C.acnes biofilms in a laboratory setting and subjected them to curcumin-PDT(curcumin combined with blue light of 180 J/cm2). Afterwards, we evaluated their viability using the XTT assay and observed them using confocal laser scanning microscopy. RESULTS: The result revealed varying resistance rates among the tested antibiotics and curcumin, with erythromycin, clindamycin, tetracycline, doxycycline, minocycline, and curcumin exhibiting resistance rates of 72 %, 44 %, 36 %, 28 %, 0 %, and 100 %, respectively. In the curcumin-PDT inhibition tests against four representative antibiotic-resistant strains, it was found that the survival rate of all strains of planktonic C. acnes was reduced, and the higher the concentration of curcumin, the lower the survival rate. Furthermore, in the biofilm inhibition tests, the vitality and three-dimensional structure of the biofilms were disrupted, and the inhibitory effect became more significant with higher concentrations of curcumin. CONCLUSION: The results emphasize the possibility of using curcumin PDT as an alternative approach for the treatment of C.acnes, especially in instances of antibiotic-resistant variations and infections related to biofilms.

Dual­directional effect of vinorelbine combined with cisplatin or fluorouracil on tumor growth and metastasis in metronomic chemotherapy in breast cancer.

Metronomic chemotherapy (MCT) regimens may be associated with risks to the patient due to the ambiguity surrounding low dosages and schedules. In the present study, metronomic regimens of vinorelbine (NVB) combined with cisplatin (CDDP) or fluorouracil (5­FU) were chosen to study the dose­response associations with tumor growth and metastasis, along with the underlying mechanisms in angiogenesis, apoptosis and tumor immunity, using experimental techniques such as immunofluorescence, immunohistochemistry, western blotting and flow cytometry. The results demonstrated a dual­directional pharmacological action of promoting and suppressing tumor growth or metastasis in BALB/c mice bearing a 4T1 tumor at certain low and high doses of the drugs. Low doses of NVB combined with CDDP or 5­FU accelerated tumor growth by enhancing angiogenesis, increasing the expression of angiogenic proteins, NF­κB and osteopontin in tumor tissues, and inducing the accumulation of myeloid­derived suppressor cells and macrophages. By contrast, higher doses inhibited tumor growth by suppressing these effects. Notably, the upregulation of apoptotic proteins was observed after low­ and high­dose treatments. Furthermore, at low concentrations, NVB combined with CDDP or 5­FU stimulated certain functions of endothelial and tumor cells, including migration and invasion, whereas at higher concentrations they suppressed proliferation and induced apoptosis. Therefore, the results of the present study suggested the potential risks of metronomic combination chemotherapy by demonstrating that, at certain low doses, tumor growth or metastasis was promoted, and emphasized the existence of an effective dose interval that changes with different drug combinations. However, further studies are needed before a specific metronomic combination regimen can be administered clinically for cancer treatment.