Flavonoids in myocardial ischemia–reperfusion injury: Therapeutic effects and mechanisms

Ischemic heart diseases are one of the major causes of death worldwide. Effective restoration of blood flow can significantly improve patients’ quality of life and reduce mortality. However, reperfusion injury cannot be ignored. Flavonoids possess well-established antioxidant properties;They also have other benefits that may be relevant for ameliorating myocardial ischemia-reperfusion injury(MIRI). In this review,we focus on flavonoids with cardiovascular-protection function and emphasize their pharmacological effects. The main mechanisms of flavonoid pharmacological activities against MIRI involve the following aspects: a) antioxidant, b) anti-inflammatory, c) anti-platelet aggregation, d) anti-apoptosis, and e)myocardial-function regulation activities. We also summarized the effectiveness of flavonoids for MIRI.     

Potentiation of microglial endocannabinoid signaling alleviates neuroinflammation in Alzheimer's disease

Alzheimer's disease (AD) isaprogressive neurodegenerative disorder characterized by chronic inflammation due to the presence of neurotoxic Aβ and tau proteins. Increased microglial activation and inflated immune response are the other factors to be considered in AD pathology. Microglial cells own biochemical machinery that synthesizes and release endocannabinoids. The exploitation of therapeutic actions of endocannabinoid system has newly emerged in the field of Alzheimer's disease. The activation of cannabinoid receptors/ cannabinoid system modulates inflammatory responses. This review assesses the association between the microglial endocannabinoid system and neuroinflammation in AD. The data supporting the anti-inflammatory role of pharmacological agents modulating cannabinoid system are also reviewed.     

Efficacy of denosumab in joint preservation for patients with giant cell tumour of the bone

BackgroundGiant cell tumour of the bone (GCTB) is an aggressive osteolytic primary tumour. GCTB is rich in osteoclast-like giant cells and contains mononuclear cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. The potential therapeutic effect of denosumab was investigated with special reference to its role in joint preservation.MethodsIn this prospective non-randomised study patients with GCTB received denosumab for 6–11 months preoperatively. Serial radiographs and biopsy and resection tumour specimens were used to monitor response to denosumab.ResultsAll 20 patients experienced pain relief in the first month of treatment. All patients demonstrated a positive radiographic response with improved subchondral and cortical bone which allowed intralesional tumour resection and preservation of the joint and articular surface in 18 cases. Histological examination following denosumab revealed rarely detectable osteoclast-like giant cells. There was an obvious increase in osteoid matrix and woven bone which showed rare RANK staining amongst the mononuclear cells and only focal RANKL positivity. At median 30 months follow-up after resection, local tumour recurrence occurred in three patients.ConclusionDenosumab provides favourable and consistent clinical, radiographic and pathologic responses which facilitates less aggressive surgical treatment, especially joint preservation. However, the local recurrence rate for GCTB following resection does not seem to be affected by denosumab and remains a concern.     

Mini-open spinal column shortening for the treatment of adult tethered cord syndrome

Tethered cord syndrome (TCS) is a challenging entity characterized by adhesions at the caudal spinal cord that prevent upward movement during growth and result in stretching of the cord with a concomitant constellation of neurologic symptoms. Although growth in height stops in adulthood, some patients still develop progressive symptoms; many underwent detethering as a child or adolescent, resulting in significant scar tissue and re-tethering. Recent strategies have focused on spinal column shortening to reduce tension on the spinal cord without exposing the previous de-tethering site. Mini-open and minimally invasive approaches avoid the large dissection and exposure associated with traditional approaches and are associated with reduced blood loss, shorter hospital stay, and similar outcomes when compared to conventional open approaches. We describe a technique for mini-open spinal column shortening. Using intraoperative navigation pedicle screws were placed at T10, T11, L1, and L2. A mini-open 3-column “egg shell” decancellation osteotomy of T12 was performed through a transpedicular approach with preservation of the superior and inferior endplates. This procedure was performed on a 28 year old male with recurrent TCS and neurogenic bladder. Postoperative imaging showed a reduction in spinal column length of 1.5 cm and evidence of decreased tension on the spinal cord. At last follow-up he was recovering well with improved urinary function. Spinal column shortening for adult TCS can be safely achieved through a mini-open approach. Future studies should compare the efficacy of this technique to both traditional de-tethering and open spinal column shortening.     

Assessment of pulmonary infectious disease treatment with Mongolian medicine formulae based on data mining, network pharmacology and molecular docking

Objective: Pulmonary infectious diseases (PID) include viral pneumonia (VP) and pulmonary tuberculosis (PT). Mongolian medicine (MM) is an effective treatment option in China, however, the core group medicines (CGMs) in the treatment of PID and their underlying therapeutic mechanisms remain unclear. In this study, through the method of data mining, the CGMs of MM for the treatment of PID were excavated, and the possible mechanism of action of the CGMs in the treatment of PID was explored by using network pharmacology. Methods: First, 89 MM formulae for the treatment of pulmonary infectious diseases collected from Gan Lu Si Bu, Meng Yi Jin Kui, People''s Republic of China Ministry of Health Drug Standards (Mongolian Medicine Volume), Standard of Mongolian Medicine Preparations in Inner Mongolia (2007 Edition), and Standard of Mongolian Medicine Preparations in Inner Mongolia (2014 Edition). The CGMs of MM for PID were excavated through association rule analysis and cluster analysis. Then, the active ingredients and potential targets of the CGMs were obtained from TCMSP, TCMIP, BATMAN-TCM databases. PID targets information was collected from OMIM, GeneCards, and DrugBank databases. The possible targets of CGMs treatment for PID were obtained by intersection. The PPI network was constructed through the STRING database, and the topology analysis of the network was performed. Through the enrichment analysis of the intersection targets by R language, the main action pathways and related target proteins of CGMs in the treatment of PID were screened out. The results were verified by molecular docking. Results: A total of 89 formulae were included, involving 164 MM herbs. The efficacy of the drugs was mainly cough-suppressing and panting-calming herbs, and heat-clearing herbs. The nature and flavor were mainly bitter and cold. The CGMs of MM to treatment of PID was excavated as the classic famous formula Sanzi Decoction (Toosendan Fructus-Chebulae Fructus-Gardeniae Fructus). A total of 28 candidate components and 237 predicted targets of CGMs were collected, and 61 common targets with PID were obtained, including key compounds such as quercetin, kaempferol, β-sitosterol and stigmastero and key targets such as VEGFA, IL6, TP53, AKT1. KEGG enrichment analysis yielded AGE-RAGE signaling pathways, IL-17 signaling pathways, and TNF signaling pathways. Molecular docking results showed that the key targets were well matched with the potential active ingredients of CGMs. Conclusion: This study found that MM commonly used cough-suppressing and panting-calming herbs in combination with heat-clearing herbs to treat PID, and the CGMs for the treatment of PID is “Toosendan Fructus-Chebulae Fructus-Gardeniae Fructus”. CGMs mainly play a role in the treatment of PID by acting on VEGFA, IL6, TP53, AKT1 and other targets, regulating AGE-RAGE signaling pathways, IL-17 signaling pathways, and TNF signaling pathways.     

Present day controversies and consensus in curettage for giant cell tumor of bone

BackgroundThe ideal treatment for giant cell tumor of bone (GCTB) is still controversial. The purpose of this study was to evaluate whether curettage was successful in the treatment of GCTB. Intralesional curettage with adjuvant therapies, such as high-speed burring, polymethylmethacrylate, phenol, ethanol, and liquid nitrogen, may be used to reduce the local recurrence rate. However, there is no consensus on the optimal use of curettage, along with fillers and adjuvants, to limit the recurrence rate.MethodsWe performed a systematic review of articles using the terms long bones, GCTB, and treatment. Case reports, reviews, opinion articles, or technique notes were excluded based on the abstract. Twenty-six articles included in this review were then studied to establish the index in suggesting the surgical treatment of GCTB.ResultsThe patient’s gender, their age, the Campanacci grade of their tumor, and the type of surgery they had were not significantly associated with the local recurrence rate. Local recurrences seemed to be associated with the site of the tumor, occurring more frequently in the proximal femur or distal radius. A pathological fracture was not a contraindication for intralesional curettage. Treatment with denosumab did not decrease the local recurrence rate in patients who had been treated with curettage.ConclusionThe current literature seems to suggest that the ideal treatment for GCTB is to remove the tumor while preserving as much of the joint as possible. Local recurrent tumors can be treated with curettage to keep the re-recurrence rate within an acceptable limit. The choice for how to treat GCTB in the proximal femur or distal radius requires special attention.