Phototherapy techniques for the management of musculoskeletal disorders: strategies and recent advances.

Musculoskeletal disorders (MSDs), which include a range of pathologies affecting bones, cartilage, muscles, tendons, and ligaments, account for a significant portion of the global burden of disease. While pharmaceutical and surgical interventions represent conventional approaches for treating MSDs, their efficacy is constrained and frequently accompanied by adverse reactions. Considering the rising incidence of MSDs, there is an urgent demand for effective treatment modalities to alter the current landscape. Phototherapy, as a controllable and non-invasive technique, has been shown to directly regulate bone, cartilage, and muscle regeneration by modulating cellular behavior. Moreover, phototherapy presents controlled ablation of tumor cells, bacteria, and aberrantly activated inflammatory cells, demonstrating therapeutic potential in conditions such as bone tumors, bone infection, and arthritis. By constructing light-responsive nanosystems, controlled drug delivery can be achieved to enable precise treatment of MSDs. Notably, various phototherapy nanoplatforms with integrated imaging capabilities have been utilized for early diagnosis, guided therapy, and prognostic assessment of MSDs, further improving the management of these disorders. This review provides a comprehensive overview of the strategies and recent advances in the application of phototherapy for the treatment of MSDs, discusses the challenges and prospects of phototherapy, and aims to promote further research and application of phototherapy techniques.

The Therapeutic Roles of Cinnamaldehyde against Cardiovascular Diseases.

Evidence from epidemiological studies has demonstrated that the incidence and mortality of cardiovascular diseases (CVDs) increase year by year, which pose a great threat on social economy and human health worldwide. Due to limited therapeutic benefits and associated adverse effects of current medications, there is an urgent need to uncover novel agents with favorable safety and efficacy. Cinnamaldehyde (CA) is a bioactive phytochemical isolated from the stem bark of Chinese herbal medicine Cinnamon and has been suggested to possess curative roles against the development of CVDs. This integrated review intends to summarize the physicochemical and pharmacokinetic features of CA and discuss the recent advances in underlying mechanisms and potential targets responsible for anti-CVD properties of CA. The CA-related cardiovascular protective mechanisms could be attributed to the inhibition of inflammation and oxidative stress, improvement of lipid and glucose metabolism, regulation of cell proliferation and apoptosis, suppression of cardiac fibrosis, and platelet aggregation and promotion of vasodilation and angiogenesis. Furthermore, CA is likely to inhibit CVD progression via affecting other possible processes including autophagy and ER stress regulation, gut microbiota and immune homeostasis, ion metabolism, ncRNA expression, and TRPA1 activation. Collectively, experiments reported previously highlight the therapeutic effects of CA and clinical trials are advocated to offer scientific basis for the compound future applied in clinical practice for CVD prophylaxis and treatment.

Advances in the therapeutic application and pharmacological properties of kinsenoside against inflammation and oxidative stress-induced disorders.

Extensive research has implicated inflammation and oxidative stress in the development of multiple diseases, such as diabetes, hepatitis, and arthritis. Kinsenoside (KD), a bioactive glycoside component extracted from the medicinal plant Anoectochilus roxburghii, has been shown to exhibit potent anti-inflammatory and anti-oxidative abilities. In this review, we summarize multiple effects of KD, including hepatoprotection, pro-osteogenesis, anti-hyperglycemia, vascular protection, immune regulation, vision protection, and infection inhibition, which are partly responsible for suppressing inflammation signaling and oxidative stress. The protective action of KD against dysfunctional lipid metabolism is also associated with limiting inflammatory signals, due to the crosstalk between inflammation and lipid metabolism. Ferroptosis, a process involved in both inflammation and oxidative damage, is potentially regulated by KD. In addition, we discuss the physicochemical properties and pharmacokinetic profiles of KD. Advances in cultivation and artificial synthesis techniques are promising evidence that the shortage in raw materials required for KD production can be overcome. In addition, novel drug delivery systems can improve the in vivo rapid clearance and poor bioavailability of KD. In this integrated review, we aim to offer novel insights into the molecular mechanisms underlying the therapeutic role of KD and lay solid foundations for the utilization of KD in clinical practice.

Changes in the Quality of Life, Psychological Status, Medication Compliance, and Prognosis of Patients with Acute Myocardial Infarction after PCI by Applying PDCA Cycle Management Model.

OBJECTIVE: To discuss the changes in the quality of life, psychological status, medication compliance, and prognosis of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) by applying plan-do-check-action (PDCA) cycle management model. METHODS: A total of 125 patients with AMI who underwent PCI in our hospital from June 2018 to June 2020 were selected and divided into control group (n = 62) and research group (n = 63) by the random number method. The conventional nursing measures were used in the control group, and the PDCA cycle management model on the basis of the control group was used in the research group. The changes in the quality of life, psychological status, medication compliance, and prognosis were observed. RESULTS: After intervention, the Generic Quality of Life Inventory-74 scores and the self-made medication compliance questionnaire score of the research group were higher than the control group (P < 0.05). After intervention, the self-rating anxiety scale score and self-rating depression scale score of the research group were lower than those of the control group (P < 0.05). The total incidence of adverse events in the research group (7.94%) was lower than that in the control group (20.97%) (P < 0.05). CONCLUSION: After the application of PDCA cycle management model, the quality of life, psychological status, medication compliance, and prognosis of AMI patients who underwent PCI were improved.

Antioxidant Therapy and Antioxidant-Related Bionanomaterials in Diabetic Wound Healing.

Ulcers are a lower-extremity complication of diabetes with high recurrence rates. Oxidative stress has been identified as a key factor in impaired diabetic wound healing. Hyperglycemia induces an accumulation of intracellular reactive oxygen species (ROS) and advanced glycation end products, activation of intracellular metabolic pathways, such as the polyol pathway, and PKC signaling leading to suppression of antioxidant enzymes and compounds. Excessive and uncontrolled oxidative stress impairs the function of cells involved in the wound healing process, resulting in chronic non-healing wounds. Given the central role of oxidative stress in the pathology of diabetic ulcers, we performed a comprehensive review on the mechanism of oxidative stress in diabetic wound healing, focusing on the progress of antioxidant therapeutics. We summarize the antioxidant therapies proposed in the past 5 years for use in diabetic wound healing, including Nrf2- and NFκB-pathway-related antioxidant therapy, vitamins, enzymes, hormones, medicinal plants, and biological materials.

Fortified phosphorus­lowering treatment through administration of lanthanum protects against vascular calcification via regulation of FGF23 in chronic kidney disease.

Phosphorus reduction can prevent against vascular calcification (VC) in chronic kidney disease (CKD), but the mechanisms underlying its actions remain unclear. The aim of the present study was to determine the effect of a fortified phosphorus­lowing treatment on VC in CKD. Serum levels of creatinine, blood urea nitrogen (BUN), fibroblast growth factor 23 (FGF23), calcium and phosphorus, and the plasma levels of parathyroid hormone (PTH) were determined in an animal model of CKD treated with or without lanthanum. Haematoxylin and eosin (H&E) staining was performed to examine the structure of kidney tissues. Western blot analysis was performed to compare the levels of total­ (t­) extracellular signal­related kinase (ERK) and phospho­ (p­)ERK among the different experimental groups to investigate the effect of FGF23 on p­ERK expression. In the animal model, administration of adenine increased the serum levels of creatinine, BUN, FGF23 and phosphorus but decreased the serum levels of calcium. In addition, adenine treatment increased the plasma levels of PTH. H&E staining showed that lanthanum treatment did not alter the severity of renal cortex injury. Furthermore, the levels of t­ERK levels did not notably differ between the Adenine­free, Adenine­vehicle and Adenine­lanthanum groups, whereas the levels of p­ERK and aortic calcium in the Adenine­vehicle group were significantly upregulated. In addition, ectopic overexpression of FGF23 increased the levels of p­ERK, Msx2 and Osx in a dose­dependent manner. Furthermore, a total of 48 patients were enrolled in the present study. In the fortified group, the serum levels of FGF23, phosphorus and PTH were significantly reduced, whereas the serum levels of calcium were significantly increased, indicating an enhanced preventative effect in the fortified group. The results of the present study suggest that FGF23 may be used as a therapeutic target in the management and prevention of VC in CKD.

Rhubarb-Aconite Decoction (RAD) Drug-Containing Serum Alleviated Endotoxin-Induced Oxidative Stress Injury and Inflammatory Response in Caco-2 Cells In Vitro.

Rhubarb-Aconite Decoction (RAD), a famous Chinese medicine prescription, has been widely used for treating intestinal injury. However, the effect of RAD on intestinal epithelial cells is unclear. The aim of this study was to investigate the effects of RAD drug-containing serum on the oxidative stress injury and inflammatory response induced by endotoxin (ET) in Caco-2 cells in vitro. Lipid peroxide malondialdehyde (MDA), lactate dehydrogenase (LDH), caspase-11, tumor necrosis factor-α(TNF-α), interleukin-3(IL-3), and cytokeratin (CK)18, adenosine triphosphate (ATP) activity, and intracellular free calcium ion levels were measured. The results showed that ET triggered the activation of caspase-11 and the massive release of TNF-α, increased the inhibitory rate of cell growth, MDA, and LDH expressions in Caco-2 cells. Moreover, RAD drug-containing serum could inhibit caspase-11 activation, decrease the release of TNF-α and IL-3, reduce intracellular free calcium ion, and enhance CK 18 expression and ATP activity. These novel findings demonstrated that ET-induced oxidative stress injury and inflammatory response of Caco-2 cells were improved by RAD drug-containing serum, indicating that RAD may be a good choice for the treatment of intestinal injury.

Ixazomib maintenance therapy in newly diagnosed multiple myeloma: An integrated analysis of four phase I/II studies.

OBJECTIVES: To evaluate the safety and efficacy of maintenance therapy with the oral proteasome inhibitor ixazomib in patients with newly diagnosed multiple myeloma (NDMM) not undergoing transplantation. METHODS: Data were pooled from four NDMM phase I/II studies; patients received induction therapy with once- or twice-weekly ixazomib plus lenalidomide-dexamethasone (IRd), melphalan-prednisone (IMP), or cyclophosphamide-dexamethasone (ICd), followed by single-agent ixazomib maintenance, given at the last tolerated dose during induction, until disease progression, death, or unacceptable toxicity. RESULTS: A total of 121 patients achieved stable disease or better after induction (weekly IRd, n = 25; twice-weekly IRd, n = 18; weekly or twice-weekly IMP, n = 35; weekly ICd, n = 43) and received ≥ 1 dose of ixazomib maintenance. Grade ≥ 3 drug-related adverse events occurred in 24% of patients during maintenance; each event was reported in ≤2% of patients. Rates of complete response were 22% after induction and 35% after maintenance. A total of 28 patients (23%) improved their response during maintenance. CONCLUSIONS: Ixazomib maintenance following ixazomib-based induction is associated with deepening of responses and a positive safety profile with no cumulative toxicity in patients with NDMM not undergoing transplantation, suggesting that ixazomib is feasible for long-term administration. Phase III investigation of ixazomib maintenance is ongoing.

Dai-Huang-Fu-Zi-Tang alleviates pulmonary and intestinal injury with severe acute pancreatitis via regulating aquaporins in rats.

BACKGROUND: Dai-Huang-Fu-Zi-Tang (DHFZT) is a famous traditional Chinese prescription with intestinal obstruction, acute pancreatitis and cholecystalgia for thousands of years. Our previous work found that DHFZT could act against pulmonary and intestinal pathological injury in rats with severe acute pancreatitis (SAP). But the underlying mechanism has not been fully elucidated. The aim of present study was to investigate whether DHFZT could relieve pulmonary and intestinal injury by regulating aquaporins after SAP induced by sodium taurocholate in rats. METHODS: Forty of SD rats were used for dose dependant experiments of DHFZT.Accurate-mass Time-of-flight liquid chromatography-mass spectrometry was used for qualitative screening of chemical compositions of DHFZT. Twenty-four rats were randomly divided into 3 groups: sham group (n = 8), model group (SAP, n = 8), DHFZT group (SAP with DHFZT treatment, n = 8). SAP models were established by retrograde injections of 5% sodium taurocholate solutions into rat pancreaticobiliary ducts. Blood samples were taken at 0, 12, 24, 48 h post-operation for detecting serum amylase, lipase, endotoxin, TNF-α, IL-6 and IL-10. Protein expression and location of aquaporin (AQP)1, 5, 8 and 9 were assessed by immunohistochemistry, western blot and immunofluorescence respectively. RESULTS: The study showed that 27 kinds of chemical composition were identified, including 10 kinds in positive ion mode and 17 kinds in negative ion mode. The results showed that AQP1, AQP5 of lung, and AQP1, AQP5, AQP8 of intestine in model group were significantly lower than that of sham group (P < 0.05), and which were obviously reversed by treatment with DHFZT. In addition, protein levels of pro-inflammatory cytokines such as TNF-α, IL-6 and endotoxin in peripheral blood were significantly suppressed by DHFZT, and that anti-inflammatory cytokine like IL-10 was just opposite. Finally, we also noted that DHFZT reduced serum levels of amylase, lipase and endotoxin, and also improved edema and pathological scores of lung and intestine after SAP. CONCLUSIONS: DHFZT ameliorated the pulmonary and intestinal edema and injury induced by SAP via the upregulation of different AQPs in lung and intestine, and suppressed TNF-α, IL-6 expression and enhanced IL-10 expression.

Calcitriol prevents peripheral RSC96 Schwann neural cells from high glucose & methylglyoxal-induced injury through restoration of CBS/H2S expression.

A meta-analysis has suggested that vitamin D deficiency is involved in diabetic peripheral neuropathy (DPN) and the levels of hydrogen sulfide (H2S) are also decreased in type 2 diabetes. The injection of vitamin D induces cystathionine-ß-synthase (CBS) expression and H2S generation. However, it remains unclear whether the supplementation of vitamin D prevents DPN through improvement of CBS/H2S expression. In the present study, RSC96 cells, a rat Schwann cell line, were exposed to high glucose and methylglyoxal (HG&MG) to simulate diabetic peripheral nerve injury in vivo. Before the exposure to HG&MG, the cells were preconditioned with calcitriol (CCT), an active form of vitamin D, and then CCT-mediated neuroprotection was investigated in respect of cellular viability, superoxide anion (O2(-)) generation, inducible nitric oxide (NO) synthase (iNOS)/NO expression, mitochondrial membrane potential (MMP), as well as CBS expression and activity. It was found that both high glucose and MGO decreased cell viability and co-treatment with the two induced a more serious injury in RSC96 cells. Therefore, the exposure to HG&MG was used in the present study. The exposure to HG&MG markedly induced iNOS expression, NO and O2(-) generation, as well as MMP loss. In addition, the exposure to HG&MG depressed CBS expression and activity in RSC96 cells. However, the preconditioning with CCT significantly antagonized HG&MG-induced cell injury including the decreased viability, iNOS overexpression, NO and O2(-) accumulation, as well as MMP loss. CCT also partially restored the decreased CBS expression and activity triggered by HG&MG, while the inhibition of CBS with hydroxylamine attenuated CCT-mediated neuroprotection. Moreover, the exogenous donation of H2S produced similar cellular protective effects to CCT. The data indicate that the supplementation of vitamin D prevents HG&MG-induced peripheral nerve injury involving the restoration of endogenous H2S system, which may provide a basal support for the treatment of DPN with vitamin D clinically.

Acupuncture for hot flashes in patients with prostate cancer.

OBJECTIVES: To determine the effect of acupuncture on hot flash frequency and intensity, quality of life, and sleep quality in patients undergoing hormonal therapy for prostate cancer. Hot flashes are a common adverse effect of hormonal therapy for prostate cancer. METHODS: Men who had a hot flash score > 4 who were receiving androgen deprivation therapy for prostate cancer underwent acupuncture with electrostimulation biweekly for 4 weeks, then weekly for 6 weeks, using a predefined treatment plan. The primary endpoint was a 50% reduction in the hot flash score after 4 weeks of therapy, calculated from the patients' daily hot flash diaries. The hot flash-related quality of life and sleep quality and biomarkers potentially related to hot flashes, including serotonin, calcitonin gene-related peptide, and urinary 5-hydroxyindoleacetic acid, were examined. RESULTS: A total of 25 men were enrolled from September 2003 to April 2007. Of these, 22 were eligible and evaluable. After 4 weeks, 9 (41%, 95% confidence interval 21%-64%) of 22 patients had had a > 50% reduction in the hot flash score. Of the 22 patients, 12 (55%, 95% confidence interval 32%-76%) met this response definition at any point during the therapy course. No patient had a significant increase in hot flash score during therapy. A reduced hot flash score was associated with improvement in the hot flash-related quality of life and sleep quality. CONCLUSIONS: Multiple placebo-controlled trials have demonstrated a 25% response rate to placebo treatment for hot flashes. Of the 22 patients, 41% had responded by week 4 and 55% overall in the present pilot study, providing evidence of a potentially meaningful benefit. Additional studies of acupuncture for hot flashes in this population are warranted.