The efficacy and safety of Yupingfeng Powder with variation in the treatment of allergic rhinitis: Study protocol for a randomized, double-blind, placebo-controlled trial

Background: Allergic rhinitis (AR) is an upper airways chronic inflammatory disease mediated by IgE, which affects 10%–20% of the population. The mainstay for allergic rhinitis nowadays include steroids and antihistamines, but their effects are less than ideal. Many patients therefore seek Chinese medicine for treatment and Yupingfeng Powder is one of the most common formulae prescribed. In this study, we aim to investigate the efficacy and safety of Yupingfeng Powder with variation for the treatment of allergic rhinitis.Study design: This is a double-blind, randomized, placebo-controlled trial. A 2-week screening period will be implemented, and then eligible subjects with allergic rhinitis will receive interventions of either “Yupingfeng Powder with variation” granules or placebo granules for 8 weeks, followed by post treatment visits at weeks 12 and 16. The change in the Total Nasal Symptom Score (TNSS) will be used as the primary outcome.Discussion: This trail will evaluate the efficacy and safety of Yupingfeng Powder in treating allergic rhinitis. The study may provide the solid evidence of Yupingfeng Powder with variation can produce better clinical efficacy than the placebo granules.Trial registration:ClinicalTrials.gov, identifier NCT04976023

Old Technique -New Evidence: Topical agents for musculo-skeletal injuries

The popular use of topical agents for the treatment of musculoskeletal injuries has persisted for centuries but not much scientific evaluations have been done. Since medicinal herbs are particularly popular in Asia, we started a systematic exploration on their choices, and their pharmacological activities; whether transcutaneous transport of bioactive components occur and above all, whether quality clinical evidences could be generated. We found that a search on the vast literature pool would reveal the favourable choices of herbal agents. Biological screening of those selected herbs showed that they probably follow three major common pathways to help with healing after injury, viz, anti-inflammation, pro-angiogenesis and cellular proliferation. Using a simple formula of selected herbs with the ideal bioactivities, evidence based clinical trials could be organized to further prove the efficacy. We have created two such formulae to be put on clinical trial. Our early pilot clinical trials on two minor injuries on the foot and one chronic inflammatory condition have yielded positive data on the value of such topical agents on pain and oedema control, as well as functional maintenance. There was also suggestion of more rapid bone healing. Although limitations exist clear with the small number of study subjects, the positive data and safe application support more studies

Repurposing hyperpolarization-activated cyclic nucleotide-gated channels as a novel therapy for breast cancer.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are members of the voltage-gated cation channel family known to be expressed in the heart and central nervous system. Ivabradine, a small molecule HCN channel-blocker, is FDA-approved for clinical use as a heart rate-reducing agent. We found that HCN2 and HCN3 are overexpressed in breast cancer cells compared with normal breast epithelia, and the high expression of HCN2 and HCN3 is associated with poorer survival in breast cancer patients. Inhibition of HCN by Ivabradine or by RNAi, aborted breast cancer cell proliferation in vitro and suppressed tumour growth in patient-derived tumour xenograft models established from triple-negative breast cancer (TNBC) tissues, with no evident side-effects on the mice. Transcriptome-wide analysis showed enrichment for cholesterol metabolism and biosynthesis as well as lipid metabolism pathways associated with ER-stress following Ivabradine treatment. Mechanistic studies confirmed that HCN inhibition leads to ER-stress, in part due to disturbed Ca2+ homeostasis, which subsequently triggered the apoptosis cascade. More importantly, we investigated the synergistic effect of Ivabradine and paclitaxel on TNBC and confirmed that both drugs acted synergistically in vitro through ER-stress to amplify signals for caspase activation. Combination therapy could suppress tumour growth of xenografts at much lower doses for both drugs. In summary, our study identified a new molecular target with potential for being developed into targeted therapy, providing scientific grounds for initiating clinical trials for a new treatment regimen of combining HCN inhibition with chemotherapy

The effectiveness of health literacy oriented programs on physical activity behaviour in middle aged and older adults with type 2 diabetes: a systematic review

Health literacy is the first step to self-management of type II diabetes mellitus, of which physical activity is the least compliant behavior. However, no reviews have summarized the effect and the process of interventions of health literacy oriented programs on physical activity behavior among middle aged and older adults with type II diabetes mellitus. This article is the first to examine the effectiveness of health literacy oriented programs on physical activity behavior among middle aged and older adults with type II diabetes mellitus. This systematic review extracted articles from nine electronic databases between 1990 and 2013. Six interventional studies were extracted and reported in accordance with the guidance of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Findings demonstrated that health literacy oriented programs increased the frequency and duration of physical activity among patients with high health literacy. Although some studies effectively improved the health literacy of physical activity, gap in literature remains open for the indistinct and unreliable measurement of physical activity within self-management programs of type II diabetes mellitus, and the questionable cross-culture generalizability of findings. Further studies with well-knit theorybased intervention with respect to patients’ cultural background, duration of intervention and objective measurements are encouraged to elucidate the relationship between health literacy oriented programs and physical activity behavior

Identification of Clinically Approved Drugs Indacaterol and Canagliflozin for Repurposing to Treat Epidermal Growth Factor Tyrosine Kinase Inhibitor-Resistant Lung Cancer

In advanced lung cancer, epidermal growth factor tyrosine kinase inhibitors (EGFR TKIs) have extraordinary clinical efficacy. However, their usefulness is severely compromised by drug resistance mediated by various mechanisms, the most important of which is the secondary EGFR T790M mutation. The mutation blocks the binding of EGFR TKIs to the receptor kinase, thereby abolishing the therapeutic efficacy. In this study, we used our free and open-source protein-ligand docking software idock to screen worldwide approved small-molecule drugs against EGFR T790M. The computationally selected drug candidates were evaluated in vitro in resistant non-small cell lung cancer (NSCLC) cell lines. The specificity of the drugs toward the mutant EGFR was demonstrated by cell-free kinase inhibition assay. The inhibition of EGFR kinase activity and its downstream signaling pathways in NSCLC cells was shown by immunoblot analysis. The positive hints were revealed to be indacaterol, canagliflozin, and cis-flupenthixol, all of which were shown to induce apoptosis in NSCLC cells harboring the EGFR T790M mutation. Moreover, the combination of indacaterol with gefitinib was also found to produce synergistic anticancer effect in NSCLC cells bearing EGFR T790M. The observed synergistic effect was likely contributed by the enhanced inhibition of EGFR and its downstream signaling molecules

The effects of a novel pilates exercise prescription method on people with non-specific unilateral musculoskeletal pain: a randomised pilot trial

Background: Pain alters the neuromuscular activation and results in altered movement adaptations. A new exercise prescription method proposes that we can restore the neuromuscular control by rehabilitating the deficient neural drive through Pilates exercises. This is done by identifying the postural control deficits using single-leg tests such as hopping, half squats and heel raises. The aim of this study was to find out if this method of prescribing exercises results in clinically relevant outcomes. Methods: Fifteen patients with chronic non-specific low back pain with unilateral musculoskeletal pain were recruited. Following consent, all patients were randomly assigned either to perform gym or Pilates-based individualised exercises once weekly for six weeks. The primary outcome was to measure the pain intensity using a 0–10 numerical rating scale. The secondary outcome measures were: the global perceived effect scale (GPE; 0–10), the patient-specific functional scale (PSFS; the patient-generated measure of disability) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC; the condition-specific measure of disability). Results: There were statistically significant differences noted after intervention within the control group in the numerical rating scale ( P =0.041), GPE ( P =0.024), PSFS ( P =0.039) and within the experimental group in the WOMAC ( P =0.008), GPE ( P =0.007) and PSFS ( P =0.007). However, as there were clinically significant baseline differences, the within-group difference could be due to regression to the mean. There were no statistically significant results between the two groups after intervention. Conclusion: This new prescription method for Pilates-based exercises may improve disability and global perception of recovery. However, the outcomes are not different from a regular gym-based exercise programme

The duality of CXCR3 in glioblastoma: unveiling autocrine and paracrine mechanisms for novel therapeutic approaches

Glioblastoma (GBM) is a highly aggressive brain tumor associated with limited therapeutic options and a poor prognosis. CXCR3, a chemokine receptor, serves dual autocrine-paracrine functions in cancer. Despite gaps in our understanding of the functional role of the CXCR3 receptor in GBM, it has been shown to hold promise as a therapeutic target for the treatment of GBM. Existing clinical therapeutics and vaccines targeting CXCR3 ligand expression associated with the CXCR3 axes have also shown anti-tumorigenic effects in GBM. This review summarizes existing evidence on the oncogenic function of CXCR3 and its ligands CXCL9, CXCL10, and CXCL11, in GBM, and examines the controversies concerning the immunomodulatory functions of the CXCR3 receptor, including immune T cell recruitment, polarization, and positioning. The mechanisms underlying monotherpies and combination therapies targeting the CXCR3 pathways are discussed. A better understanding of the CXCR3 axes may lead to the development of strategies for overcoming the limitations of existing immunotherapies for GBM. </p