Acupuncture for obesity and related diseases: Insight for regulating neural circuit.

Obesity is defined as abnormal or excessive fat accumulation that may impair health. Obesity is associated with numerous pathological changes including insulin resistance, fatty liver, hyperlipidemias, and other obesity-related diseases. These comorbidities comprise a significant public health threat. Existing anti-obesity drugs have been limited by side effects that include depression, suicidal thoughts, cardiovascular complications and stroke. Acupuncture treatment has been shown to be effective for treating obesity and obesity-related conditions, while avoiding side effects. However, the mechanisms of acupuncture in treating obesity-related diseases, especially its effect on neural circuits, are not well understood. A growing body of research has studied acupuncture's effects on the endocrine system and other mechanisms related to the regulation of neural circuits. In this article, recent research that was relevant to the use of acupuncture to treat obesity and obesity-related diseases through the neuroendocrine system, as well as some neural circuits involved, was summarized. Based on this, acupuncture's potential ability to regulate neural circuits and its mechanisms of action in the endocrine system were reviewed, leading to a deeper mechanistic understanding of acupuncture's effects and providing insight and direction for future research about obesity. Please cite this article as: Jiang LY, Tian J, Yang YN, Jia SH, Shu Q. Acupuncture for obesity and related diseases: insight for regulating neural circuit. J Integr Med. 2024; 22(2): 93-101.

Direct Access to Thio- and Seleno-acetamides Bearing (Benzo)thiazoles by a Base-Promoted One-Pot Two-Step Three-Component Reaction of 2-Amino(benzo)thiazoles with Aryl Acetyl Chlorides and Dichalcogenides.

Highly efficient and practical carbon-chalcogen (S, Se) and amide bonds formation methodologies for the synthesis of thio- and seleno-acetamides were developed, via the base-promoted one-pot two-step reactions of 2-amino(benzo)thiazoles and aryl acetyl chlorides with dichalcogenides. This cross-coupling reaction afforded the goal products that had been chalcogenated regioselectively in moderate to good yields. Further transformations of the new synthesized compounds, DFT calculations and preliminary mechanism studies are discussed as well.

Effect of Platelet-Rich Plasma at Different Initiation Times on Healing of the Bone-Tendon Interface of the Rotator Cuff in a Mouse Model.

Background: Platelet-rich plasma (PRP) has demonstrated beneficial effects on healing of the bone-tendon interface (BTI). Purpose: To determine the optimal initiation time for PRP application after rotator cuff repair in an animal model. Study Design: Controlled laboratory study. Methods: A total of 136 C57BL/6 mice were included; 40 mice were used to prepare PRP, while 96 mice underwent acute supraspinatus tendon (SST) repair. The animals were randomly divided into 4 groups: a control group and 3 groups in which PRP was injected into the injury interface immediately after surgery, on the 7th postoperative day (PRP-7d), and on the 14th postoperative day. At 4 and 8 weeks postoperatively, the animals were sacrificed, blood was collected by eyeball removal, and samples of the SST-humerus complex were collected. Histological, imaging, immunological, and biomechanical data were compared among the groups using 1-way analysis of variance with the Bonferroni post hoc test. Results: Histological analysis revealed that the fibrocartilage layer at the BTI was larger in the PRP-7d group compared to the other groups at both 4 and 8 weeks postoperatively. Moreover, the PRP-7d group exhibited improved proteoglycan content and distribution compared to the other groups. Enzyme-linked immunosorbent assay results demonstrated that at 4 weeks postoperatively, higher concentrations of transforming growth factor-ß1 and platelet-derived growth factor-BB (PDGF-BB) were seen in the PRP-7d group versus the PRP-14d and control gruops (P < .05), and at 8 weeks postoperatively, the concentration of PDGF-BB was higher in the PRP-7d group versus the control group (P < .05). Biomechanical testing at 4 weeks postoperatively revealed that the failure load and ultimate strength of the SST-humerus complex were superior in the PRP-7d group compared to the other groups (P < .05), at 8 weeks, PRP-7d group was superior to the control group (P < .05). Additionally, at 8 weeks postoperatively, the PRP-7d group exhibited a greater trabecular number and trabecular thickness at the BTI compared to the PRP-14d and control gruops (P < .05). Conclusion: PRP promoted healing of the BTI after a rotator cuff injury at an early stage. Clinical Relevance: A PRP injection on the 7th postoperative day demonstrated superior therapeutic effects compared with injections at other time points.

Abnormal Lower Limb Biomechanics During a Bilateral Vertical Jump Despite the Symmetry in Single-Leg Vertical Hop Height in Athletes After ACL Reconstruction.

Background: A limb symmetry index (LSI) of >90% for single-leg horizontal hop distance is recommended as a cutoff point for safe return to sports after anterior cruciate ligament reconstruction (ACLR). Despite achieving this threshold, abnormal lower limb biomechanics continue to persist in athletes after ACLR. Symmetry in single-leg vertical hop height appears to be more difficult to achieve and can be a better representation of knee function than single-leg horizontal hop distance. Purpose: To explore whether an LSI of >90% for single-leg vertical hop height can represent normal lower limb biomechanics in athletes during a bilateral vertical jump after ACLR. Study Design: Controlled laboratory study. Methods: According to the LSI for single-leg vertical hop height, 46 athletes who had undergone ACLR with an autologous ipsilateral bone-patellar tendon-bone or hamstring tendon graft were divided into a low symmetry group (LSI <90%; n = 23) and a high symmetry group (LSI >90%; n = 23), and 24 noninjured athletes were selected as the control group. The kinematic and kinetic characteristics during a bilateral vertical jump were compared between the low symmetry, high symmetry, and control groups. Results: During the propulsion phase of the bilateral vertical jump, the operated side in the high symmetry group showed a lower knee extension moment than the nonoperated side (P = .001). At peak vertical ground-reaction force, the operated side in the high symmetry group showed a lower knee internal rotation moment compared with the control group (P = .016). Compared with the nonoperated side, the operated side in the high symmetry group showed a higher hip extension moment (P = .002), lower knee extension moment (P < .001), lower ankle plantarflexion moment (P < .001), and lower vertical ground-reaction force (P = .023). Conclusion: Despite achieving an LSI of >90% for single-leg vertical hop height, athletes after ACLR showed abnormal lower limb biomechanical characteristics during the bilateral vertical jump. Clinical Relevance: Symmetrical single-leg vertical hop height may not signify ideal biomechanical or return-to-sports readiness in this population.

Effects of Kinesio taping on lower limb biomechanical characteristics during unexpected jumping in patients with chronic ankle instability.

PURPOSE: The current biomechanical research on the application of Kinesio taping (KT) to patients with chronic ankle instability (CAI) has focused on testing the expected movements. However, unexpected movements are more common in actual sports. Therefore, the present study aimed to investigate the effects of KT on the biomechanical characteristics of the knee and ankle joints during unexpected jumping movements. METHODS: Twenty-one patients with unilateral CAI were recruited to capture the biomechanical parameters during unexpected jumping movements under different interventions: no taping (NT), placebo taping (PT), and KT. A one-way repeated measures analysis of variance was used to compare the differences in knee and ankle biomechanical characteristics among patients with CAI between the three intervention conditions. RESULTS: At initial contact, the KT group demonstrated a significant decrease in ankle plantarflexion and knee flexion angles compared to the NT group (p < 0.05). At the early landing phase, the KT group had a significant increase in peak ankle dorsiflexion angle, peak ankle eversion angle, peak ankle dorsiflexion moment, and peak ankle eversion moment compared to the NT and PT groups (p < 0.05). Furthermore, the KT group had a significantly reduced peak knee flexion angle, peak knee eversion angle, and peak vertical ground reaction force (p < 0.05) compared to the NT and PT groups. CONCLUSION: KT significantly improves the sprain-prone touchdown posture of patients with CAI. And reducing the risk of ankle sprains during the early landing phase by promoting ankle dorsiflexion and eversion angles and moments.

Electroacupuncture Alleviates Obesity and Insulin Resistance via the GLP-1-VTADA Reward Circuit.

INTRODUCTION: We investigated the effects of electroacupuncture (EA) on improving obesity and insulin resistance (IR) in high-fat diet-induced (HFDI) obese rats by modulating the nucleus tractus solitarius (NTS) glucagon-like peptide-1 (GLP-1)-ventral tegmental area (VTA) dopamine (DA) neural reward circuit, thereby uncovering a possible central mechanism underlying EA's actions in improving obesity and IR. METHODS: We randomly allocated 45 Wistar male rats to five groups (normal, model, EA, chemogenetic activation, chemogenetic suppression + EA), with 9 rats in each group. All interventions were conducted within 8 weeks after the model was established. We tested rats for obesity phenotypes included body mass, Lee's index, 24-h food intake, and glucose-metabolism parameters. We observed protein and gene expression for GLP-1 in the NTS and tyrosine hydroxylase in the VTA by Western blotting and real-time polymerase chain reaction, as well as their localization by immunofluorescence. We also determined the DA content in the VTA using high-performance liquid chromatography. RESULTS: Obese rats exhibited marked hyperphagia, accompanied by increased excitability of DA neurons in the VTA region and reduced insulin sensitivity. After EA treatment, obese rats showed augmented excitability of NTS GLP-1 and suppression of VTADA neurons with a diminution in food intake, showing results similar to those in the chemogenetic activation group. After EA treatment and while inhibiting GLP-1 neurons by chemogenetics, the effect of EA on activating GLP-1 neurons and inhibiting VTADA was partially abrogated. The effects of improving obesity and insulin sensitivity were likewise also suppressed. CONCLUSION: EA effectively activated GLP-1 neurons in the NTS, thereby inhibited the expression of DA in the VTA and improved obesity and insulin sensitivity in HFDI-obese rats.

Efficacy of Platelet-Rich Plasma in the Treatment of Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis.

BACKGROUND: The probiological healing effect of platelet-rich plasma (PRP) during tissue repair has recently gathered much attention. This study aimed to conduct a systematic review and meta-analysis of patients with diabetic foot ulcer (DFU) receiving PRP or conventional treatment to evaluate their efficacy. METHODS: PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases were comprehensively searched by 2 independent reviewers following PRISMA guidelines for the inclusion of randomized controlled trials (RCTs) comparing PRP with conventional treatments for DFUs. The primary measurements of healing rate and healing time, the methodological quality and extracted data were assessed using Review Manager 5.3. Statistical significance was set at P < 0.05. RESULTS: A total of 10 RCTs involving 550 patients were included in this study, PRP was observed to significantly improve the healing rate (risk ratio [RR] = 1.38, 95% confidence interval [CI] 1.05-1.82, P = 0.02) and shorten the healing time (mean difference [MD] = -23.23, 95% CI -45.97 to -0.49, P = 0.05) of patients with DFU when compared to the conventional treatment. CONCLUSIONS: Compared to conventional treatment, PRP effectively promoted the healing of patients with DFU by evidently improving the healing rate and healing time.

Eccentric Contraction Enhances Healing of the Bone-Tendon Interface After Rotator Cuff Repair in Mice.

BACKGROUND: Various muscle contraction modalities have differing effects on the musculoskeletal system. To understand the magnitude of these effects, the authors investigated the effects of eccentric and concentric contractions on the bone-tendon interface after rotator cuff repair in mice. HYPOTHESIS: Eccentric contraction promotes healing of the bone-tendon interface after rotator cuff repair in mice better than other muscle contraction patterns. STUDY DESIGN: Controlled laboratory study. METHODS: The authors performed acute supraspinatus tendon repair of the right shoulder in 104 C57BL/6 mice. Animals were randomized into 4 groups postoperatively: control group (Con group), horizontal running group (Horz group), +15° uphill running group (Up group), and -15° downhill running group (Down group), with 26 animals in each group. At 4 and 8 weeks postoperatively, the authors removed the eyeball, collected blood samples, and extracted the supraspinatus tendon-humerus complex for histological, immunological, bone morphological, and biomechanical tests. RESULTS: At 4 and 8 weeks postoperatively, the Down group exhibited a better collagen cell arrangement and fibrocartilage layer than the other 3 groups. At 4 weeks postoperatively, anti-inflammatory macrophages (M2 macrophages) were observed at the repair site in all groups except for the Con group. At 8 weeks postoperatively, M2 macrophages were withdrawn from the tendon site in all groups. The transforming growth factor ß1 concentration in the Down group was greater than that in the other 3 groups at 4 weeks postoperatively, and it was higher than that in the Con group at 8 weeks postoperatively. The bone volume fraction, number of trabeculae, and thickness of trabeculae at the repair site in the Down group, as well as the ultimate strength and failure load in the biomechanical tests, were greater than those in the other 3 groups at 8 weeks postoperatively. CONCLUSION: Eccentric contraction promotes healing of the bone-tendon interface after rotator cuff repair in mice better than other muscle contraction patterns. CLINICAL RELEVANCE: After clinical rotator cuff repair, patients can be rehabilitated by eccentric training to speed up the functional recovery of the shoulder joint.

[Electroacupuncture improves obesity and promotes white adipose tissue browning by regulating central glucagon-like peptide-1].

OBJECTIVE: To observe the effect of electroacupuncture （EA） on white adipose tissue （WAT） browning by regulating central glucagon-like peptide-1 （GLP-1）, so as to explore the possible central mechanisms of EA in improving obesity. METHODS: Thirty male Wistar rats were randomly divided into normal group, model group, EA group, HM3D group, and EA+HM4D group, with 6 rats in each group. The obesity rat model was obtained by feeding with high-fat diet for 8 weeks. Adeno-associated virus combined with DREADDs was injected into bilateral nucleus of solitary tract （NTS）, with rAAV-GLP-1+rAAV-4D applied to the EA+HM4D group, rAAV-GLP-1+rAAV-3D applied to the HM3D group, and rAAV-GLP-1+rAAV-GFP applied to other 3 groups. After modeling, rats in the EA and EA+HM4D groups received EA treatment at bilateral "Zusanli"（ST36）, "Fenglong"（ST40）, "Guanyuan"（CV4） and "Zhongwan"（CV12）, with successive waves （2 Hz, 1 mA） for 10 minutes, 3 times a week, for a total of 8 weeks. Body mass of rats in each group were measured before and 2, 4, 6, and 8 weeks after intervention. Abdominal and perirenal WAT mass was weighed, serum triglyceride （TG） and total cholesterol （TC） contents were detected by using automatic analyzer, and nonestesterified fatty acid （NEFA） content was detected by using colorimetric assay kit. The morphology of abdominal WAT lipid droplets was observed by HE staining. The mRNA expressions of GLP-1 in NTS, AMPK in ventromedial nucleus of hypothalamus（VMH）, UCP1 and PGC-1α in subcutaneous fat were detected by real-time PCR. The protein expression levels of GLP-1, AMPK, phosphorylated-AMPK, UCP1 and PGC-1α were detected by Western blot. The activation level of GLP-1 neurons in NTS was observed by immunofluorescence. RESULTS: Compared with the normal group, abdominal WAT lipid droplets were enlarged, body weight, serum TG, TC, NEFA contents, abdominal and perirenal WAT mass, mRNA and protein expression levels of AMPK were significantly increased（P<0.01, P<0.05）, while GLP-1 neurons activation level, mRNA and protein expression levels of GLP-1, UCP1 and PGC-1α, and AMPK protein phosphorylation were decreased （P<0.01） in the model group. After EA intervention, body weight at 6 and 8 weeks after intervention and other indexes mentioned above were all significantly reversed （P<0.01, P<0.05） in the EA group in comparison with those of the model group. Compared with the EA group, the HM3D group had reduced abdominal WAT lipid droplets size, decreased serum TG, TC, and NEFA contents, and protein expression level of AMPK（P<0.01, P<0.05）, with increased mRNA and protein expression levels of GLP-1, UCP1 and PGC-1α, and phosphorylation level of AMPK protein（P<0.01, P<0.05）, while the EA+HM4D group had enlarged abdominal WAT lipid droplets, increased body weight 6 and 8 weeks after intervention, abdominal and renal WAT mass, and NEFA content （P<0.01, P<0.05）, with decreased serum TG content, activation level of GLP-1 neurons in the NTS, mRNA and protein expression levels of GLP-1, UCP1 and PGC-1α （P<0.01, P<0.05）, as well as down-regulated phosphorylation of AMPK protein and mRNA （P<0.01, P<0.05）. CONCLUSION: EA can effectively promote the browning of WAT, which may be related to the activation of GLP-1 neurons in the NTS, as well as the promotion of the phosphorylation of AMPK in the VMH and up-regulation of UCP1.

Can Symmetry of Single-Leg Vertical Jump Height Represent Normal Lower Limb Biomechanics of Athletes After Anterior Cruciate Ligament Reconstruction?

BACKGROUND: After anterior cruciate ligament reconstruction (ACLR), single-leg horizontal hop distance limb symmetry index (LSI) >90% is recommended as a cutoff point for safe return to sport (RTS). However, athletes after ACLR have abnormal lower limb biomechanics despite an adequate single-leg hop distance LSI, implying that athletes are at high risk of reinjury. Symmetry of single-leg vertical jump height appears to be more difficult to achieve and can be a better representation of knee function than single-leg horizontal hop distance. HYPOTHESIS: Athletes after ACLR with single-leg jump height LSI >90% had similar biomechanical characteristics to healthy athletes. STUDY DESIGN: Controlled laboratory study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 46 athletes after ACLR were divided into low jump height (LJH, jump height LSI <90%, n = 23) and high jump height (HJH, jump height LSI >90%, n = 23) groups according to symmetry of single-leg vertical jump height, while 24 healthy athletes acted as a control (CONT) group. One-way analysis of variance was used to compare the kinematic and kinetic characteristics of the LJH, HJH, and CONT groups during single-leg vertical jump. RESULTS: Both the LJH and HJH groups demonstrated greater limb asymmetry (lower LSI) during landing compared with the CONT group in knee extension moment (P < 0.05), peak knee flexion angle (P < 0.05), and knee power (P < 0.05). CONCLUSION: Symmetry in single-leg vertical jump height does not represent normal lower limb biomechanics in athletes after ACLR. CLINICAL RELEVANCE: Symmetrical jump height may not signify ideal biomechanical or RTS readiness, but single-leg vertical jump test can be used as a supplement to horizontal hop test or other functional tests to reduce the likelihood of false-negative results in the absence of detailed biomechanical evaluation.

Efficacy of platelet-rich plasma and platelet-rich fibrin in arthroscopic rotator cuff repair: A systematic review and meta-analysis.

OBJECTIVE: Basic scientific studies have demonstrated positive effects of platelet-rich therapies, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), on tendon repair. However, clinical evidence indicating improved prognosis is controversial. In this study, we aimed to determine whether augmentation of arthroscopic rotator cuff repair with PRP and PRF improves outcomes compared to arthroscopic repair alone. LITERATURE SURVEY: PubMed, Embase, and Cochrane library databases were comprehensively searched for randomized controlled trials (RCTs) published until June 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. No language restriction was applied. METHODOLOGY: The primary outcomes were the rate of repeat tears after arthroscopic rotator cuff repair (retear rate) and clinical function scores (Constant-Murley Score, University of California, Los Angeles Score), and the extracted data were assessed for quality. Statistical analyses were performed using Review manager 5.3, and p < .05 was considered statistically significant. SYNTHESIS: Ten RCTs with 628 patients were included. The results showed that augmenting surgery with PRP reduces retear rates compared to surgery alone (risk ratio [RR] = 0.40, 95% confidence interval [CI] 0.23-0.69, p = .001), whereas PRF has no effect on retear rates (p = .92). Regarding clinical function, PRP improves Constant-Murley scores (mean difference [MD] = 2.03, 95% CI 0.13-3.93, p = .04) and University of California, Los Angeles scores (MD = 1.30, 95% CI 0.36-2.24, p = .007), whereas PRF improves only Constant-Murley scores (MD = 3.93, 95% CI 1.50-6.36, p = .002). However, these differences were small and below the minimum clinically important difference threshold. CONCLUSIONS: This study showed that compared to arthroscopic rotator cuff repair alone, the application of PRP in arthroscopic rotator cuff repair reduces retear rate and improves clinical function scores, whereas the application of PRF has no clinically meaningful benefit. The small number and heterogeneity of studies as well as methodological limitations and risk of bias limit confidence in the true effect.

The role of GPLD1 in chronic diseases.

Glycosylphosphatidylinositol-specific phospholipase D (GPLD1) is a specific enzyme for glycosylphosphatidylinositol (GPI) anchors, thereby exerting its biological functions by cleaving membrane-associated GPI molecules. GPLD1 is abundant in serum, with a concentration of approximately 5-10 µg/mL. Previous studies have demonstrated that GPLD1 plays a crucial role in the pathogenesis of numerous chronic diseases including disorders of lipid and glucose metabolism, cancer, and neurological disorders. In the present study, we reviewed the structure, functions, and localization of GPLD1 in chronic diseases, as well as exercise-mediated regulation of GPLD1, thus providing a theoretical support to develop GPLD1 as a new therapeutic target for chronic diseases.

Comparison of the effects of platelet-rich plasma and corticosteroid injection in rotator cuff disease treatment: a systematic review and meta-analysis.

HYPOTHESIS: Platelet-rich plasma (PRP) and corticosteroids are used to treat rotator cuff diseases. However, few reviews have compared the effects of these 2 treatments. In this study, we compared the effects of PRP and corticosteroid injection on the prognosis of rotator cuff diseases. MATERIALS AND METHODS: According to the Cochrane Manual of Systematic Review of Interventions, the PubMed, Embase, and Cochrane databases were searched comprehensively. Two independent authors screened suitable studies and performed data extraction and risk of bias assessment. Only randomized controlled trials comparing the effects of PRP and corticosteroid in the treatment of rotator cuff injuries were included, as measured by clinical function and pain during different follow-up periods. RESULTS: Nine studies with 469 patients were included in this review. In short-term treatment, corticosteroids were superior to PRP in the improvement of Constant, Simple Shoulder Test, and American Shoulder and Elbow Surgeons scores (mean difference [MD] -5.08, 95% confidence interval [CI] -10.26, 0.06; P = .05 and MD -0.97, 95% CI -1.68, -0.07; P = .03 and MD -6.67, 95% CI -12.85, -0.49; P = .03, respectively). No statistically significant difference was observed between the 2 groups at midterm (P > .05), and the recovery of the Simple Shoulder Test and American Shoulder and Elbow Surgeons scores in PRP treatment was significantly better than that in corticosteroid treatment in the long term (MD: 1.21, 95% CI: 0.68, 1.74; P < .00001 and MD: 6.96, 95% CI: 3.90, 9.61; P < .00001, respectively). In pain reduction based on visual analog scale score, corticosteroids led to better pain reduction (MD: 0.84, 95% CI: 0.03, 1.64; P = .04), but no significant difference was observed in pain reduction between the 2 groups in the any term (P > .05). However, these differences did not reach the minimum clinically important difference. CONCLUSIONS: Current analysis showed that corticosteroids have better efficacy in short term, whereas PRP is more beneficial for long-term recovery. However, no difference was observed in the mid-term efficacy between the 2 groups. Randomized controlled trials with longer follow-up periods and larger sample sizes are also needed to determine the optimal treatment.

Scalp electroacupuncture targeting the VTADA neurons to relieve negative emotions and promote the alleviation of chronic pain.

Object: Chronic pain and negative emotions are often linked, and both can impact the reward circuit. The use of electroacupuncture (EA) has been found to regulate and improve these conditions. This study explores the potential mechanism of chronic pain relief by adding acupoints with emotional regulation effect to the basis of routine EA analgesia, to optimize the acupoint compatibility scheme of EA in the treatment of analgesia. Method: For this study, 42 male Wistar rats were used. Recombinant adeno-associated viruses were used to label and regulate the activity of dopamine (DA) neurons. The rat model was established by complete Freund's adjuvant (CFA). Lower limb electroacupuncture (LEA) was applied to the ST36 and BL60 acupoints. In addition, LEA + scalp EA (SEA) was given using the GV20 and GV24+ acupoints besides ST36 and BL60. To evaluate the pain threshold, we measured 50% paw withdrawal thresholds and thermal paw withdrawal latencies. Negative emotions were evaluated through the open field test, marble-burying test, sucrose preference test, and forced swimming test. Moreover, the conditional place preference test was conducted to measure the reward behavior in response to pain relief. Immunofluorescence staining, Western blotting, and qPCR were used to detect the activity of the VTADA-NAc reward circuit. Result: The injection of CFA significantly lowered the pain threshold. As the pain persisted, the anxiety and depression-like behaviors escalated while the response to reward reduced. Meanwhile, the VTADA-NAc pathway was suppressed with pain chronification. However, activating DA neurons in VTA attenuated the effects induced by CFA. LEA could relieve chronic pain, negative emotions, and reward disorders, while also activating the VTADA-NAc pathway. In addition, LEA + SEA exhibited a more pronounced effect compared with LEA alone. Nevertheless, chemogenetic inhibition of DA neurons decreased the efficacy of LEA + SEA in the treatment of chronic pain and associated comorbidities. Conclusion: Adding SEA to conventional LEA effectively alleviates negative emotions and chronic pain, potentially due to the activation of the VTADA-NAc reward neural circuit. Thus, LEA + SEA is a more effective treatment for hyperalgesia and associated negative emotions compared with LEA alone.

Pea Peptide Supplementation in Conjunction With Resistance Exercise Promotes Gains in Muscle Mass and Strength.

It is generally considered that protein supplementation and resistance exercise significantly increase muscle mass and muscle growth. As the hydrolysis products of proteins, peptides may play the crucial role on muscle growth. In this study, male rats were orally administrated 0.4 g/kg body weight of pea peptide combined with 8 weeks of moderate intensity resistance exercise training. After treatment, the body gains, upper limb grip, muscle thickness, and wet weight of biceps brachii were tested, and the cross-sectional area of biceps brachii muscle fiber and the types of muscle fibers were determined by HE staining, immunofluorescence staining, and lactate dehydrogenase activity, respectively. Western blot analysis was used to investigate the level of growth-signaling pathway-related proteins. The results showed that pea peptide supplementation combined with resistance exercise training significantly increased body weight, upper limb grip, muscle thickness, wet weight of biceps brachii, and cross-sectional area of muscle fiber. Meanwhile, pea peptide supplementation obviously elevated the ratio of fast-twitch fiber (type II) and the expression of muscle growth-signaling pathway-related proteins. In addition, the PP2 oligopeptide in pea peptide with the amino acid sequence of LDLPVL induced a more significant promotion on C2C12 cell growth than other oligopeptides.

Leukocyte-rich and Leukocyte-poor Platelet-rich Plasma in Rotator Cuff Repair: A Meta-analysis.

To systematically review of randomized controlled trials (RCTs) to compared the effects of leukocyte-rich and leukocyte-poor platelet-rich plasma in arthroscopic rotator cuff repair. Two independent reviewers comprehensively searched PubMed, Embase, and Cochrane library databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comparison of leukocyte-rich platelet-rich plasma or leukocyte-poor platelet-rich plasma in rotator cuff repair in a level I RCTs. Methodological quality assessment was carried out using Cochrane Review Manager 5.3 software. P<0.05 was considered statistically significant. Nine RCTs with 540 patients were included in this review. Meta-analysis showed that leukocyte-poor platelet-rich plasma in significantly reduced retear rate in rotator cuff repair [RR=0.56 95% CI (0.42, 0.75); P<0.05), and in clinical results, the constant score [MD=3.67, 95% CI (1.62, 5.73); P=0.0005], UCLA score [MD=1.60, 95% CI (0.79, 2.42); P=0.0001], ASES score [MD=2.16, 95% CI (0.12, 4.20); P=0.04] were significantly improved. There was a significant result in favor of PRP for the Constant score [MD=-1.24, 95% CI (-1.50, -0.99); P<0.00001], while SST scores were not significantly different among all groups [MD=0.21, 95% CI (-0.21, 0.64); P=0.32]. In conclusion, leukocyte-poor platelet-rich plasma can improved the clinical function and reduced retear rate in arthroscopic rotator cuff repair. In contrast, the efficacy of leukocyte-rich platelet-rich plasma was not significantly improved with the exception of VAS score.

Effects of leukocyte-rich platelet-rich plasma and leukocyte-poor platelet-rich plasma on the healing of bone-tendon interface of rotator cuff in a mice model.

Platelet-rich plasma (PRP) is widely used clinically to treat tendon injuries, and often contains leukocytes. However, the debate regarding the concentration of leukocytes in PRP is still ongoing. This study aimed to evaluate the therapeutic effects of leukocyte-rich platelet-rich plasma (LR-PRP) and leukocyte-poor platelet-rich plasma (LP-PRP) on the healing of the bone-tendon interface (BTI) of the rotator cuff. A total of 102 C57BL/6 mice were used. Thirty mice were used to prepare the PRP, while 72 underwent acute supraspinatus tendon injury repair. The animals were then randomly assigned to three groups: LR-PRP, LP-PRP and control groups. The mice were euthanized at 4 and 8 weeks postoperatively, and histological, immunological and biomechanical analyses were performed. The histological results showed that the fusion effect at the bone-tendon interface at 4 and 8 weeks after surgery was greater in the PRP groups and significantly increased at 4 weeks; however, at 8 weeks, the area of the fibrocartilage layer in the LP-PRP group increased significantly. M2 macrophages were observed at the repaired insertion for all the groups at 4 weeks. At 8 weeks, M2 macrophages withdrew back to the tendon in the control group, but some M2 macrophages were retained at the repaired site in the LR-PRP and LP-PRP groups. Enzyme-linked immunoassay results showed that the concentrations of IL-1ß and TNF-α in the LR-PRP group were significantly higher than those in the other groups at 4 and 8 weeks, while the concentrations of IL-1ß and TNF-α in the LP-PRP group were significantly lower than those in the control group. The biomechanical properties of the BTI were significantly improved in the PRP group. Significantly higher failure load and ultimate strength were seen in the LR-PRP and LP-PRP groups than in the control group at 4 and 8 weeks postoperatively. Thus, LR-RPR can effectively enhance the early stage of bone-tendon interface healing after rotator cuff repair, and LP-PRP could enhance the later stages of healing after rotator cuff injury.

Effect of Mechanical Stimulation Combined With Platelet-Rich Plasma on Healing of the Rotator Cuff in a Murine Model.

BACKGROUND: Mechanical stimulation and platelet-rich plasma (PRP) have been shown to be beneficial for healing of the bone-tendon interface (BTI), but few studies have explored the efficacy of a combination of these applications. We investigated the effect of mechanical stimulation combined with PRP on rotator cuff repair in mice. HYPOTHESIS: Mechanical stimulation combined with PRP can enhance BTI healing in a murine model of rotator cuff repair. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 160 C57BL/6 mice were used. Overall, 40 mice were used to prepare PRP, while 120 mice underwent acute supraspinatus tendon (SST) repair. The animals were randomly assigned to 4 groups: control group, mechanical stimulation group, PRP group, and mechanical stimulation combined with PRP group (combination group). At 4 and 8 weeks postoperatively, animals were sacrificed, the eyeballs were removed to collect blood, and the SST-humeral complexes were collected. Histological, biomechanical, immunological, and bone morphometric tests were performed. RESULTS: Histologically, at 4 and 8 weeks after surgery, the area of the fibrocartilage layer at the BTI in the combination group was larger than in the other groups. The content and distribution of proteoglycans in this layer in the combination group were significantly greater than in the other groups. At 8 weeks postoperatively, trabecular number, and trabecular bone thickness of the subchondral bone area of interest at the BTI of the combination group were greater than those of the other groups, bone volume fraction of the combination group was greater than the control group. On biomechanical testing at 4 and 8 weeks after surgery, the failure load and ultimate strength of the SST-humeral complex in the combination group were higher than in the other groups. Enzyme-linked immunosorbent assay results showed that, at 4 weeks postoperatively, the serum concentrations of transforming growth factor beta 1 and platelet-derived growth factor (PDGF) in the combination group were significantly higher than in the other groups; at 8 weeks, the PDGF-AB concentration in the combination group was higher than in the control and mechanical stimulation groups. CONCLUSION: Mechanical stimulation combined with PRP can effectively promote the early stage of healing after a rotator cuff injury. CLINICAL RELEVANCE: These findings imply that mechanical stimulation combined with PRP can serve as a potential therapeutic strategy for rotator cuff healing.

Sea Cucumber Intestinal Peptide Induces the Apoptosis of MCF-7 Cells by Inhibiting PI3K/AKT Pathway.

Sea cucumbers are one of many marine echinoderm animals that contain valuable nutrients and medicinal compounds. The bioactive substances in sea cucumbers make them have promising biological and pharmacological properties, including antioxidant, anti-bacterial, and anti-tumor effects. In this study, sea cucumber intestinal peptide (SCIP) is a small molecular oligopeptide (<1,000 Da) extracted from sea cucumber intestines hydrolyzed by alkaline protease. The analysis of amino acid composition showed that hydrophobic amino acids and branched-chain amino acids were rich in SCIP. Nowadays, although increasing studies have revealed the biological functions of the sea cucumber active substances, there are few studies on the function of SCIP. Furthermore, due to the anti-cancer activity being an essential characteristic of sea cucumber active substances, we also investigated the anti-cancer potential and the underlying mechanism of SCIP in vivo and in vitro. The results indicate that SCIP inhibits the growth of MCF-7 tumor cells in zebrafish and increases the apoptosis of human breast cancer MCF-7 cells. Further mechanism studies confirm that SCIP promotes the expression of apoptosis-related proteins and thus promotes the breast cancer cells (MCF-7) apoptosis via inhibition of PI3K/AKT signal transduction pathway.