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.

Gallic acid ameliorates endometrial hyperplasia through the inhibition of the PI3K/AKT pathway and the down-regulation of cyclin D1 expression.

BACKGROUND: Gallic acid (GA) is an organic compound with phenolic properties that occurs naturally and can be found in Guizhi Fuling capsules, showcasing a wide range of biological functionalities. PURPOSE: The objective of this study was to examine the influence of GA on endometrial hyperplasia (EH) and elucidate its underlying mechanism. METHODS: Initially, the induction of EH was achieved by administering estradiol to mice via continuous subcutaneous injection for a duration of 21 days. Concurrently, GA treatment was administered, and subsequently, the uterine tissue structure was assessed using hematoxylin and eosin (H&E) staining. Following this, the proliferation of human endometrial cells treated by GA was determined utilizing the CCK-8 method. Furthermore, network pharmacology and single-cell-RNA-seq data were employed to identify the target of GA action. In addition, we will employ immunofluorescence (IF), immunohistochemistry (IHC), flow cytometry, western blot and RT-qPCR methodologies to investigate the impact of GA on the expression level of cyclin D1, PI3K, p-PI3K, AKT, p-AKT. RESULTS: GA treatment ameliorated histopathological alterations in the uterus and suppress proliferation. Estradiol stimulation can activate the PI3K/AKT pathway, leading to up-regulation of cyclin D1 expression, whereas GA treatment results in down-regulation of its expression. CONCLUSIONS: The expression of cyclin D1 is down-regulated by GA through the inhibition of the PI3K/AKT pathway, effectively mitigating estradiol-induced EH in mice.

Cyanine based ratio fluorescent probe and its application in hypochlorite detection.

Hypochlorite (ClO-), a weakly acidic reactive oxygen species, plays a crucial role in antibacterial and anti-inflammatory defense mechanisms. However, elevated levels of ClO- or disruptions in endogenous sites can lead to tissue damage and various diseases including cardiovascular disease, neuronal degeneration, and arthritis. To address this, the development of a specific fluorescent probe with a built-in self-calibration ratio mode for the analysis and biological imaging of ClO- is essential. In this study, a cyanine-based fluorescent probe (Cy-H) was designed for ratiometric fluorescent detection of ClO-, utilizing its aggregation behavior as a novel approach in this field. Upon exposure to ClO-, the phenolic hydroxyl group in probe Cy-H was oxidized into benzoquinone, leading to the formation of cyanine products that displayed a strong tendency to aggregate. As a result, the maximum emission peak of the probe shifted from 700 nm to 485 nm. Notably, a linear relationship was observed between the peak intensity ratio (I485/I700) and the concentration of hypochlorite, with a limit of detection (LOD) of 0.49 µM. Furthermore, this probe was successfully employed for imaging analysis of hypochlorite in living cells and zebrafish.

Immobilization of Pb in waste water and soil by tourmaline-biochar composites (TBs): Characteristics and mechanisms.

Novel tourmaline-biochar composites (TBs) were synthesized by introducing tourmaline (TM) into pomelo peel biochar (BC). The surface properties of TBs and BC were studied and the adsorption performances for Pb2+ were investigated. Compared to pristine BC, the adsorption ability for Pb2+ on TBs was enhanced with the increase of TM in TBs, and up to 514.62 mg/g on 5%TB. The enrichment of inorganic metals caused by TM in TBs made the precipitation and cation ion exchange become the main mechanisms in adsorbing Pb2+, and the amounts of adsorbing Pb2+ by those two mechanisms on TBs were 1.10-1.48 times and 1.20-1.30 times those of BC, respectively. Furthermore, applying TBs to practical contaminated soil increased the soil pH and electrical conductivity (EC) after 15 days of incubation. The increased content of residual-Pb and reduced exchangeable-Pb and DTPA-Pb indicated that TBs were favorable for the immobilization of Pb in soil. This study gives a new perspective on the synthesis of tourmaline-biochar composite and their application in Pb-polluted water and soil.

The double-edged role of neutrophil heterogeneity in inflammatory diseases and cancers.

Neutrophils are important immune cells act as the body's first line of defense against infection and respond to diverse inflammatory cues. Many studies have demonstrated that neutrophils display plasticity in inflammatory diseases and cancers. Clarifying the role of neutrophil heterogeneity in inflammatory diseases and cancers will contribute to the development of novel treatment strategies. In this review, we have presented a review on the development of the understanding on neutrophil heterogeneity from the traditional perspective and a high-resolution viewpoint. A growing body of evidence has confirmed the double-edged role of neutrophils in inflammatory diseases and tumors. This may be due to a lack of precise understanding of the role of specific neutrophil subsets in the disease. Thus, elucidating specific neutrophil subsets involved in diseases would benefit the development of precision medicine. Thusly, we have summarized the relevance and actions of neutrophil heterogeneity in inflammatory diseases and cancers comprehensively. Meanwhile, we also discussed the potential intervention strategy for neutrophils. This review is intended to deepen our understanding of neutrophil heterogeneity in inflammatory diseases and cancers, while hold promise for precise treatment of neutrophil-related diseases.

Design, synthesis and antifreeze properties of biomimetic peptoid oligomers.

Ice crystals can cause great damage. The utilization of antifreeze agents is an efficient method to prevent or reduce ice crystal formation and growth. Synthetic antifreeze agents are toxic and have low efficiency, and natural antifreeze proteins suffer from high cost and low stability. Here, we have designed and synthesized a series of peptoid oligomers by mimicking the antifreeze protein structure, and the structure-property relationship was also studied. The reported peptoids here have excellent antifreeze properties and are nontoxic to cells. These novel peptoid materials have great potential to replace current commonly used antifreeze agents, such as dimethyl sulfoxide, and become a new generation of antifreeze agents applied in cryopreservation.

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.

A FRET Based Composite Sensing Material Based on UCNPs and Rhodamine Derivative for Highly Sensitive and Selective Detection of Fe3.

The existence of excessive concentration of iron ion (Fe3+) in water will do harm to the environment and biology. Presently, sensitive and selective determination of Fe3+ directly in real environment samples is still a challenging job because of the high complexity of the sample matrix. In this work, we reported a new sensor system for Fe3+ based on fluorescence resonance energy transfer (FRET) from upconversion nanoparticles (UCNPs) to Rhodamine derivative probe (RhB). The NaYF4: Yb, Er@SiO2@P(NIPAM-co-RhB) nanocomposites was constructed, in which PNIPAm was used as the probe carrier. The nanocomposites can not only be excited by infrared light to avoid the interference of background light in the Fe3+ detection process, but also enhance the detection signal output through temperature control. Under the optimum conditions, the RSD (Relative standard deviation) of actual sample measurements ranges was from 1.95% to 4.96%, with the recovery rate from 97.4% to 103.3%, which showed high reliability for Fe3+ detection. This work could be extended to sensing other target ions or molecules and may promote the widespread use of FRET technique.

Re-Du-Ning injection ameliorates radiation-induced pneumonitis and fibrosis by inhibiting AIM2 inflammasome and epithelial-mesenchymal transition.

BACKGROUND: Radiation-induced lung injury (RILI) is a common side effect in chest radiotherapy patients, and there is no good medicine to treat it. Re-Du-Ning (RDN) injection is a traditional Chinese medicine that is clinically used to treat upper respiratory tract infections and acute bronchitis. RDN has the advantage of high safety and mild side effects. The mechanism of most traditional Chinese medicine preparations is unknown. PURPOSE: To illustrate the mechanisms of RDN for the treatment of RILI. METHODS: Female C57BL/6 mice were used to establish a RILI model via irradiation, and RDN injection was intraperitoneally administered at doses of 5, 10, and 20 ml/kg. The cytokines were measured by ELISA and qPCR. The data related to Absent in melanoma 2 (AIM2) inflammasome were analyzed via ELISA and a network pharmacological approach. In addition, the data related to epithelial-mesenchymal transition (EMT) were analyzed via immunofluorescence, Western blotting, and a network pharmacological approach. RESULTS: RDN robustly alleviated RILI. Meanwhile, RDN downregulated inflammatory cells' infiltration and the expression of pro-inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α. Next, the potential molecular mechanisms of RDN were predicted through network pharmacology analysis. RDN may ameliorate radiation pneumonitis (RP) by inhibiting AIM2-mediated pyroptosis. Moreover, RDN treatment inhibited EMT and phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) pathway. The active compounds from Lonicera japonica Thunb. decreased the phosphorylation of Akt. CONCLUSION: These findings demonstrate that RDN, as a traditional Chinese medicine preparation, will be a candidate drug for treating RILI.

A specific upregulated long noncoding RNA in colorectal cancer promotes cancer progression.

Long noncoding RNA (lncRNA) plays a crucial role in the pathogenesis of various diseases, including colorectal cancer (CRC). The gene mutations of adenomatous polyposis coli (APC) were found in most patients with CRC. They function as important inducers of tumorigenesis. Based on our microarray results, we identified a specific upregulated lncRNA in CRC (SURC). Further analysis showed that high SURC expression correlated with poorer disease-free survival and overall survival in patients with CRC. Furthermore, we found that mutated APC genes can promote the transcription of SURC by reducing the degradation of ß-catenin protein in CRC. Functional assays revealed that knockdown of SURC impaired CRC cell proliferation, colony formation, cell cycle, and tumor growth. Additionally, SURC promotes CCND2 expression by inhibiting the expression of miR-185-5p in CRC cells. In conclusion, we demonstrate that SURC is a specific upregulated lncRNA in CRC and the SURC/miR-185-5p/CCND2 axis may be targetable for CRC diagnosis and therapy.

Poly(ε-Caprolactone)-Methoxypolyethylene Glycol (PCL-MPEG)-Based Micelles for Drug-Delivery: The Effect of PCL Chain Length on Blood Components, Phagocytosis, and Biodistribution.

Background: The main challenge of polymeric micelles as drug delivery systems is that the actual delivery efficiency is not as high as expected, which is closely related with the interactions with the complex biological environments such as blood components, phagocytosis, and biodistribution. Herein, we expect to understand these concerns for the clinically relevant micelles that composed of methoxypolyethylene glycol (MPEG) with identical chain length And poly(ε-caprolactone) (PCL) with tunable chain length (PCLn-MPEG) (n=20, 30, and 40) wherein doxorubicin was encapsulated as a model drug. Methods: The doxorubicin-loaded PCLn-MPEG micelles were prepared by a dialysis method and characterized by dynamic light scattering and transmission electron microscopy. The surface PEG density and chain conformation were investigated by dissipative particle dynamics simulation. The stability of the micelles was detected by nanoparticle tracking analysis. The effects of PCL chain length on the blood components, phagocytosis, and biodistribution were assayed in vitro and in vivo. Results: The micelles exhibited spherical morphology with a diameter about 30nm. The PEG chain conformation from "mushroom-like" to "brush-like" was evident. The micelles have no remarkable effect on the red blood cells, blood coagulation, and platelet activation. Interestingly, the protein adsorption was affected and dependent on the chain conformation, with lowest adsorption for PCL30-MPEG, which also has the loWest phagocytosis. The stability of the micelles was in the order of PCL40-MPEG>PCL30-MPEG>PCL20-MPEG which was dependent on the PCL chain length. The micelles mainly accumulated in liver, with the order consistent with their stability, indicating that, besides the phagocytosis, the stability of the micelle plays an important role in biodistribution as well. The related mechanisms were proposed and discussed. Conclusion: Manipulating the PEG/PCL ratio of the micelle is an effective approach to modulate the protein adsorption, phagocytosis, and biodistribution, which may be a prerequisite for clinical applications.

MRI and DC/TMD Methods Analyze the Diagnostic Accuracy of the Change in Articular Disc of Temporomandibular Joint.

METHODS: DC/TMD clinical questionnaire diagnosis was conducted for 30 patients with temporomandibular disorder (TMD) and 11 asymptomatic volunteers who were admitted to the Department of Oral Medicine of the First Hospital affiliated with Jinan University from June 2020 to June 2021. At the same time, MRI scanned the opening and closed positions to obtain the image information of the articular disc and compared the diagnostic difference between MRI and DC/TMD to the position of the articular disc through statistical analysis. RESULTS: The probability of DC/TMD's diagnosis of reusable/nonreusable anterior disc displacement (ADD) was 80.1% and 62.7%, respectively. CONCLUSION: DC/TMD's diagnosis of abnormal articular disc position is less accurate than MRI testing. Therefore, the diagnosis of these two diseases for DC/TMD examination is of little significance, and MRI examination is required at the same time. It can improve diagnosis specificity and sensitivity, reduce missed diagnosis and misdiagnosis rates to ensure that true positive patients can be detected in time, and establish a basis for clinical diagnosis and treatment.

The role of lncRNAs in the tumor microenvironment and immunotherapy of melanoma.

Melanoma is one of the most lethal tumors with highly aggressive and metastatic properties. Although immunotherapy and targeted therapy have certain therapeutic effects in melanoma, a significant proportion of patients still have drug resistance after treatment. Recent studies have shown that long noncoding RNAs (lncRNAs) are widely recognized as regulatory factors in cancer. They can regulate numerous cellular processes, including cell proliferation, metastasis, epithelial-mesenchymal transition (EMT) progression and the immune microenvironment. The role of lncRNAs in malignant tumors has received much attention, whereas the relationship between lncRNAs and melanoma requires further investigation. Our review summarizes tumor suppressive and oncogenic lncRNAs closely related to the occurrence and development of melanoma. We summarize the role of lncRNAs in the immune microenvironment, immunotherapy and targeted therapy to provide new targets and therapeutic methods for clinical treatment.

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.

Rosuvastatin Nanomicelles Target Neuroinflammation and Improve Neurological Deficit in a Mouse Model of Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH), a devastating subtype of stroke, has a poor prognosis. However, there is no effective therapy currently available due to its complex pathological progression, in which neuroinflammation plays a pivotal role in secondary brain injury. In this work, the use of statin-loaded nanomicelles to target the neuroinflammation and improve the efficacy was studied in a mouse model of ICH. METHODS: Rosuvastatin-loaded nanomicelles were prepared by a co-solvent evaporation method using polyethylene glycol-poly(ε-caprolactone) (PEG-PCL) copolymer as a carrier. The prepared nanomicelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), and then in vitro and in vivo studies were performed. RESULTS: TEM shows that the nanomicelles are spherical with a diameter of about 19.41 nm, and DLS shows that the size, zeta potential, and polymer dispersity index of the nanomicelles were 23.37 nm, -19.2 mV, and 0.221, respectively. The drug loading content is 8.28%. The in vivo study showed that the nanomicelles significantly reduced neuron degeneration, inhibited the inflammatory cell infiltration, reduced the brain edema, and improved neurological deficit. Furthermore, it was observed that the nanomicelles promoted the polarization of microglia/macrophages to M2 phenotype, and also the expression of the proinflammatory cytokines, such as IL-1ß and TNF-α, was significantly down-regulated, while the expression of the anti-inflammatory cytokine IL-10 was significantly up-regulated. The related mechanism was proposed and discussed. CONCLUSION: The nanomicelles treatment suppressed the neuroinflammation that might contribute to the promoted nerve functional recovery of the ICH mouse, making it potential to be applied in clinic.

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.

[Highlights of the Chinese guideline on sublingual immunotherapy for allergic rhinitis and asthma（English edition）].

The Chinese guideline on sublingual immunotherapy（SLIT） for allergic rhinitis and asthma（English edition） has been developed by a panel of experts on behalf of the Chinese Society of Allergy, and published in December 2019. The guideline is herein organized to outline the critical items, including the epidemiology of allergic rhinitis and asthma, clinical application and mechanisms of SLIT, standardized procedure, indications and contraindications, therapeutic process, and future perspective, to guide and improve the clinical practice of SLIT.

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.

Copper Sulfide Nanoparticles-Incorporated Hyaluronic Acid Injectable Hydrogel With Enhanced Angiogenesis to Promote Wound Healing.

Skin wound caused by trauma, inflammation, surgery, or burns remains a great challenge worldwide since there is no effective therapy available to improve its clinical outcomes. Herein, we report a copper sulfide nanoparticles-incorporated hyaluronic acid (CuS/HA) injectable hydrogel with enhanced angiogenesis to promote wound healing. The prepared hydrogel could not only be injected to the wound site but also exhibited good photothermal effect, with temperature increasing to 50°C from room temperature after 10 min of near-infrared light irradiation. The cell culture experiments also showed that the hydrogel has no cytotoxicity. In the rat skin wound model, the hydrogel treated wounds exhibited better healing performances. Masson's trichrome staining suggested that collagen deposition in wounds treated with the hydrogel was significantly higher than other groups. The immunohistochemical staining showed that the hydrogel can effectively upregulate the expression of vascular endothelial growth factor (VEGF) in the wound area at the incipient stage of healing, and the CD 31 immunofluorescence staining confirmed the enhanced angiogenesis of the hydrogel. Taken together, the prepared CuS/HA hydrogel can effectively increase the collagen deposition, upregulate the expression of VEGF, and enhance the angiogenesis, which may contribute to promote wound healing, making it a promising for application in treating skin wound.

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.