Role of Trace Cadmium Exposure on the Development of Occlusal Traumatic Temporomandibular Arthritis.

OBJECTIVE: To investigate whether heavy metal cadmium acts as a risk factor for temporomandibular joint disorder disease and to study its pathogenic mechanism. METHODS: A total of 57 rats were allocated into 6 distinct groups, distinguished by 2 interventions: occlusal elevation and cadmium water gavage. These groups included a blank control group, occlusal elevation group, occlusal elevation + 0.42 mg/mL cadmium water gavage group, occlusal elevation + 4.2 mg/mL cadmium water gavage group, no occlusal elevation + 0.42 mg/mL cadmium water gavage group, and no occlusal elevation + 4.2 mg/mL cadmium water gavage group. The impact of cadmium exposure on cartilage oxidative stress was evaluated through the assessment of SOD, CAT, GST, and GSH-Px enzyme activities. In addition, the influence of cadmium exposure on alterations in the extracellular matrix and inflammatory mediators was examined by analyzing the expression levels of type II collagen, protein aggregation polysaccharide, glycosaminoglycan, IL1ß, IL-6, and TNF-α. Histologic examination of the condylar process cartilage of rats in the occlusal elevation + cadmium water gavage group was conducted to ascertain the occurrence of osteoarthritis. RESULTS: The variance in the expression levels of inflammatory factors did not demonstrate statistical significance between the occlusal elevation group and the blank control group; however, statistical significance was observed between the occlusal elevation + cadmium water gavage group and both the control and occlusal elevation groups. CONCLUSION: The severity of inflammation and condylar lesions correlates directly with the concentration of cadmium.

Activation of Wnt/ß-catenin signalling is required for TGF-ß/Smad2/3 signalling during myofibroblast proliferation.

Fibrosis in animal models and human diseases is associated with aberrant activation of the Wnt/ß-catenin pathway. Despite extensive research efforts, effective therapies are still not available. Myofibroblasts are major effectors, responsible for extracellular matrix deposition. Inhibiting the proliferation of the myofibroblast is crucial for treatment of fibrosis. Proliferation of myofibroblasts can have many triggering effects that result in fibrosis. In recent years, the Wnt pathway has been studied as an underlying factor as a primary contributor to fibrotic diseases. These efforts notwithstanding, the specific mechanisms by which Wnt-mediated promotes fibrosis reaction remain obscure. The central role of the transforming growth factor-ß (TGF-ß) and myofibroblast activity in the pathogenesis of fibrosis has become generally accepted. The details of interaction between these two processes are not obvious. The present investigation was conducted to evaluate the level of sustained expression of fibrosis iconic proteins (vimentin, α-SMA and collagen I) and the TGF-ß signalling pathway that include smad2/3 and its phosphorylated form p-smad2/3. Detailed analysis of the possible molecular mechanisms mediated by ß-catenin revealed epithelial-mesenchymal transition and additionally demonstrated transitions of fibroblasts to myofibroblast cell forms, along with increased activity of ß-catenin in regulation of the signalling network, which acts to counteract autocrine TGF-ß/smad2/3 signalling. A major outcome of this study is improved insight into the mechanisms by which epithelial and mesenchymal cells activated by TGFß1-smad2/3 signalling through Wnt/ß-catenin contribute to lung fibrosis.

Various Sequence Types of Escherichia coli Isolates Coharboring blaNDM-5 and mcr-1 Genes from a Commercial Swine Farm in China.

Sixteen different sequence types (STs) of Escherichia coli isolates from a commercial swine farm in China were confirmed to coharbor the carbapenem resistance gene blaNDM-5 and the colistin resistance gene mcr-1 Whole-genome sequencing revealed that blaNDM-5 and mcr-1 were located on a 46-kb IncX3 plasmid and a 32-kb IncX4 plasmid, respectively. The two plasmids can transfer together with a low fitness cost, which might explain the presence of various STs of E. coli coharboring blaNDM-5 and mcr-1.

High-Mobility Group Box 1 Mediates Epithelial-to-Mesenchymal Transition in Pulmonary Fibrosis Involving Transforming Growth Factor-ß1/Smad2/3 Signaling.

Epithelial-to-mesenchymal transition (EMT) is a crucial event in the cellular origin of myofibroblasts that secrete extracellular matrix in the progression of pulmonary fibrosis (PF). High-mobility group box 1 (HMGB1) is a novel mediator of EMT. However, whether this process involves the recognized transforming growth factor-ß1 (TGF-ß1)/Smad signaling that also contributes to EMT in PF has not yet been elucidated. Here, we developed a model of PF induced by bleomycin (BLM) in rats and conducted several simulation experiments in A549 (human) and RLE-6TN (rat) alveolar epithelial cell (AEC) lines to unravel the role of TGF-ß1/Smad2/3 signaling in HMGB1-mediated EMT. We found that the levels of serum HMGB1 and lung hydroxyproline were severely elevated after BLM administration. Moreover, the protein expression of HMGB1, TGF-ß1, phosphorylated Smad2/3 (p-Smad2/3), and mesenchymal markers including α-smooth muscle actin, vimentin, and type I collagen were significantly increased with the reduced protein expression of an epithelial marker (E-cadherin) in the rat model by Western blot or immunohistochemical analysis. In addition, the uptake of both exogenous TGF-ß1 and HMGB1 by AECs could induce EMT; meanwhile, HMGB1 dramatically enhanced TGF-ß1 expression and triggered Smad2/3 phosphorylation. In contrast, TGF-ß1 deficiency evidently ameliorated HMGB1-mediated EMT with reduced p-Smad2/3 in A549 cells. It provides new insights that HMGB1 release from injured lungs promotes AEC damage through induction of the EMT process, in which TGF-ß1/Smad2/3 signaling is activated and contributes to PF. These results suggest that HMGB1 may constitute a therapeutic target for developing antifibrotic agents for abnormal lung remodeling.

Oral immunotherapy with enteric-coated capsules for allergic rhinitis caused by house dust mites.

Background: Oral immunotherapy (OIT) is a promising allergen-specific approach in the management of food allergy; however, studies on OIT for allergic rhinitis (AR) have rarely been reported. The purpose of this study is to evaluate the efficacy and safety of OIT using enteric-coated capsules for AR induced by house dust mites. Methods: A total of 49 patients with AR were enrolled, including 25 who received subcutaneous immunotherapy (SCIT) and 24 who received OIT. The clinical efficacy and safety in both groups were evaluated. Results: After 1 year of treatment, both SCIT and OIT demonstrated significant therapeutic effects. OIT was found to be more effective than SCIT in reducing the total AR symptom score and improving the results of nasal provocation tests. Local and systemic adverse reactions were observed in the SCIT group, while none were reported in the OIT group. Conclusion: OIT is an effective and safe treatment for mite-induced AR.

Application in the analysis of the occlusal force of free-end missing tooth implant restoration with T-SCAN III.

Introduction: The occlusal force of the teeth in the dental arch and the remaining adjacent natural teeth will change after implant restoration with a free-end missing tooth. This study intends to use the T-SCAN III scanner to collect dynamic quantitative data before and after the restoration of free-end implants and to explore the application of the T-SCAN III in redistributing the occlusal force of free-end implants. Methods: In this study, 24 patients with free-end implant restoration were selected, and their occlusion was tested before, immediately after, and 3 months after implant restoration. Results: In all 24 cases, the bite force of the first natural tooth adjacent to the implanted tooth after restoration changed from 19.12% ± 9.48%-12.93% ± 11.47% (p < 0.01). For additional data analysis, all cases were further subdivided by single implant and fixed bridge restorations. In 17 cases, there was a successful follow-up after 3 months. The percentage of the total bite force of dental arch with implant increased from 41.92% ± 10.78%-53.06% ± 10.71% (p < 0.01). Discussion: This study shows that the free-end implant restoration protects the remaining natural teeth, and the patient's missing dental arch bite force improves within 3 months of implant restoration.

Mitochondrial Dysfunction in Chronic Respiratory Diseases: Implications for the Pathogenesis and Potential Therapeutics.

Mitochondria are indispensable for energy metabolism and cell signaling. Mitochondrial homeostasis is sustained with stabilization of mitochondrial membrane potential, balance of mitochondrial calcium, integrity of mitochondrial DNA, and timely clearance of damaged mitochondria via mitophagy. Mitochondrial dysfunction is featured by increased generation of mitochondrial reactive oxygen species, reduced mitochondrial membrane potential, mitochondrial calcium imbalance, mitochondrial DNA damage, and abnormal mitophagy. Accumulating evidence indicates that mitochondrial dysregulation causes oxidative stress, inflammasome activation, apoptosis, senescence, and metabolic reprogramming. All these cellular processes participate in the pathogenesis and progression of chronic respiratory diseases, including chronic obstructive pulmonary disease, pulmonary fibrosis, and asthma. In this review, we provide a comprehensive and updated overview of the impact of mitochondrial dysfunction on cellular processes involved in the development of these respiratory diseases. This not only implicates mechanisms of mitochondrial dysfunction for the pathogenesis of chronic lung diseases but also provides potential therapeutic approaches for these diseases by targeting dysfunctional mitochondria.

Chronic Obstructive Pulmonary Disease Treatment and Pharmacist-Led Medication Management.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death across the globe. Its repeated exacerbation will seriously worsen the quality of life, aggravate the patients' symptoms, and bring a heavy burden on the patients and the society. Understanding the current status of drug therapy and the role of pharmaceutical care is essential for the management of COPD. In addition to the drugs already on the market, recent clinical trials also show that emerging novel drugs for treating COPD are being developed to prevent the symptoms, reduce the frequency of acute exacerbation, and improve the quality of life. Recent progress in new drug research should lead to novel treatment options for COPD patients in future clinical practice. The pharmaceutical care has shown significantly favourable impacts on addressing drug-related problems, supporting its vital role in the management of COPD, especially when there are a wide range of therapeutic agents. This review not only provides an overview of current treatment strategies but also further underlines the importance of new drug development and pharmaceutical care for patients with COPD.

Efficacy of a 3-year course of sublingual immunotherapy for mite-induced allergic rhinitis with a 3-year follow-up.

Aim: To evaluate the long-term efficacy of sublingual immunotherapy (SLIT) in treating mite-sensitized allergic rhinitis (AR). Materials & methods: 150 AR children were randomly divided into SLIT and pharmacotherapy (PT) groups, receiving a 3-year course of SLIT along with PT or PT only. Results: The symptom and medication scores at the 3- and 6-year follow-up were significantly lower compared with the baseline levels in both groups, while the values were significantly lower in SLIT group than in PT group. No significant differences were observed between 3- and 6-year follow-up in SLIT group. Conclusion: 3-year SLIT along with PT appeared more effective compared with PT only for mite-induced AR in children, and the treatment was effective for at least 3 consecutive years even after SLIT ceased.

Lianhua Qingwen prescription for Coronavirus disease 2019 (COVID-19) treatment: Advances and prospects.

BACKGROUND: An outbreak of Coronavirus Disease 2019 (COVID-19) which was infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is still spreading and has led to unprecedented health emergency over the world. Though no specific drug has been developed so far, emerging agents have been confirmed effective or potentially beneficial to restrain it. Lianhua Qingwen (LHQW) is a commonly used Chinese medical preparation to treat viral influenza, including in the fight against SARS in 2002-2003 in China. Recent data also showed that LHQW played a vigorous role in COVID-19 treatment. PURPOSE: This review will elucidate the pre-clinical and clinical evidence of LHQW in lung protection and antiviral activities, and provide timely data delivery for the exploration of effective treatment strategies in the therapy of COVID-19. STUDY DESIGN AND METHOD: The research data were obtained from the academic databases (up to August 8, 2020) including Pubmed, CNKI and Web of Science, on ethnobotany and ethno medicines. The search keywords for screening the literature information were "virus", "COVID-19", or "SARS-CoV-2", and "Lianhua Qingwen". The documents were filtered and summarized for final evaluation. RESULTS: The collected evidence demonstrated that LHQW exhibited benefits against COVID-19. Impressively, LHQW in conjunction with conventional treatment could significantly improve COVID-19 patients as a synergetic strategy. The mechanisms were mainly involved the antiviral activity, and regulation of inflammation response as well as immune function. CONCLUSION: Although the data were far from adequate, the latest advances had shown the benefits of LHQW in COVID-19, especially in combination with other antiviral drugs. This review provides comprehensive evidence of LHQW as a complementary strategy for treating COVID-19. Nevertheless, imperious researches should be conducted to clarify the unconfirmed effects, regulatory mechanisms and adverse reactions of LHQW in treating COVID-19 by means of well designed randomized controlled trials.

Berberine-Incorporated Shape Memory Fiber Applied as a Novel Surgical Suture.

The surgical suture has long been used to reconnect the injured tissues to restore their structure and function. However, its utility remains challenging in many areas, such as surgical site infections and minimally invasive surgeries. Herein, we report a novel surgical suture that possesses both antibacterial activity and shape memory effect to address these issues. In detail, natural antibacterial berberine was incorporated directly into the spinning solution of shape memory polyurethane with a near body transition temperature, and then berberine-containing polyurethane (BP) fibers were prepared by a facile one-step wet-spinning method for surgical suture. The prepared BP fibers were micro-sized and characterized by their transition temperature, morphology, water contact angles, mechanical properties, in vitro shape memory effect, drug release, and antibacterial activity. The results showed that with the increasing amount of the incorporated berberine, the transition temperatures of the fibers were not significantly affected, remains at near body temperature, while the contact angles of the fibers were significantly decreased and the mechanical properties of the fibers were significantly weakened. The optimized fiber was selected to evaluate the cytotoxicity and in vivo biocompatibility before in vivo shape memory effect and wound healing capacity in a mouse skin suture-wound model was tested. Besides the shape memory effect, it was demonstrated that the fiber is capable of antibacterial activity and anti-inflammatory effect, and promoting wound healing. The mechanism of the antibacterial activity and anti-inflammatory effect of the fiber was discussed. Overall, it is expected that by the berberine added to the fiber for surgical suture, it will be more popular and extend the utility of the sutures in a wide range of clinical applications.

Astragaloside IV Improves Bleomycin-Induced Pulmonary Fibrosis in Rats by Attenuating Extracellular Matrix Deposition.

Pulmonary fibrosis is a devastating lung disorder with mysterious pathogenesis and limited treatment options. It is well-recognized that the uncontrolled proliferation of lung fibroblasts and differentiation of fibroblasts into myofibroblasts excessively produce extracellular matrix (ECM) proteins which contribute to the fibrosis change of the lungs. Thus, blocking ECM accumulation would delay fibrosis progression. In this study, we observed the effects of astragaloside IV (ASV) (10 mg/kg/d) on ECM proteins in bleomycin (BLM, 5 mg/kg)-treated rats. Our results showed that ASV not only ameliorated BLM-induced body weight loss, lung coefficient increase, histological changes and collagen secretion, but also reduced the levels of type III collagen (Col-III) in lung homogenate, laminin (LN) and hyaluronic acid (HA) in serum, as well as hydroxyproline (HYP) in lung tissue. Besides, ASV significantly down-regulated the levels of high-mobility group box1 (HMGB1) in serum and lung tissue, and inhibited the up-regulated expression of α-SMA (marker of myofibroblasts) in the lungs. Taken together, these findings indicate that ASV attenuates BLM-induced ECM deposition, supporting its use as a promising candidate to treat lung fibrosis.

Total Glucosides of Danggui Buxue Tang Attenuate BLM-Induced Pulmonary Fibrosis via Regulating Oxidative Stress by Inhibiting NOX4.

Pulmonary fibrosis (PF) is a serious chronic lung disease with unknown pathogenesis. Researches have confirmed that oxidative stress which is regulated by NADPH oxidase-4 (NOX4), a main source of reactive oxygen species (ROS), is an important molecular mechanism underlying PF. Previous studies showed that total glucosides of Danggui Buxue Tang (DBTG), an extract from a classical traditional Chinese herbal formula, Danggui Buxue Tang (DBT), attenuated bleomycin-induced PF in rats. However, the mechanisms of DBTG are still not clear. We hypothesize that DBTG attenuates PF through regulating the level of oxidative stress by inhibiting NOX4. And we found that fibrosis indexes hydroxyproline (HYP) and type I collagen (Col-I) were lower in DBTG groups compared with the model group. In addition, the expression of transforming growth factor-ß1 (TGF-ß1) and expression of alpha smooth muscle actin (α-SMA) were also much more decreased than the model group. For oxidative stress indicators, DBTG blunted the decrease of superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), and the increase in malondialdehyde (MDA), 8-iso-prostaglandin in lung homogenates. Treatment with DBTG restrained the expression of NOX4 compared to the model group. Present study confirms that DBTG inhibits BLM-induced PF by modulating the level of oxidative stress via suppressing NOX4.

Inositol-requiring protein 1 - X-box-binding protein 1 pathway promotes epithelial-mesenchymal transition via mediating snail expression in pulmonary fibrosis.

Epithelial-mesenchymal transition (EMT) is a complex biological program during which cells loss epithelial phenotype and acquire mesenchymal features. EMT is thought to be involved in the pathogenesis of various fibrotic diseases including pulmonary fibrosis (PF). Recent studies suggest that endoplasmic reticulum (ER) stress is associated with EMT in the progression of PF. However, the exact mechanism is unclear. Here, we developed a PF model with bleomycin (BLM) administration in rats and conducted several simulation experiments in alveolar epithelial cell (AECs) RLE-6TN to unravel the role of inositol-requiring protein 1 (IRE1) - X-box-binding protein 1 (XBP1) signal pathway in ER stress-induced EMT in PF. First, we observed that ER stress was occurred in type II AECs accompanied by EMT in BLM-induced PF. Then we explored the role of IRE1-XBP1-snail pathway in transforming growth factor (TGF)-ß1/tunicamycin (TM)-induced EMT. When TGF-ß1/TM was treated on AECs, IRE1 and XBP1 were overexpressed, meanwhile, snail expression was upregulated accompanied with EMT. However, when IRE1 or XBP1 was knockdown, TGF-ß1/TM-induced EMT were blocked while the expression of snail was inhibited. Then we silenced snail and found that TGF-ß1/TM-induced EMT were also suppressed, but it had no effect on the up-regulated expression of IRE1 and XBP1. Thus, we concluded that IRE1-XBP1 pathway promotes EMT via mediating snail expression in PF.