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Diabetic cardiomyopathy (DCM) is a prevalent complication of type 2 diabetes (T2D). 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is a glycolysis regulator. However, the potential effects of PFKFB3 in the DCM remain unclear. In comparison to db/m mice, PFKFB3 levels decreased in the hearts of db/db mice. Cardiac-specific PFKFB3 overexpression inhibited myocardial oxidative stress and cardiomyocyte apoptosis, suppressed mitochondrial fragmentation, and partly restored mitochondrial function in db/db mice. Moreover, PFKFB3 overexpression stimulated glycolysis. Interestingly, based on the inhibition of glycolysis, PFKFB3 overexpression still suppressed oxidative stress and apoptosis of cardiomyocytes in vitro, which indicated that PFKFB3 overexpression could alleviate DCM independent of glycolysis. Using mass spectrometry combined with co-immunoprecipitation, we identified optic atrophy 1 (OPA1) interacting with PFKFB3. In db/db mice, the knockdown of OPA1 receded the effects of PFKFB3 overexpression in alleviating cardiac remodeling and dysfunction. Mechanistically, PFKFB3 stabilized OPA1 expression by promoting E3 ligase NEDD4L-mediated atypical K6-linked polyubiquitination and thus prevented the degradation of OPA1 by the proteasomal pathway. Our study indicates that PFKFB3/OPA1 could be potential therapeutic targets for DCM. [ABSTRACT FROM AUTHOR]

Peptide‐based supramolecular therapeutics (PST) refer to those theranostic nanomedicines based on peptide or peptide derivatives self‐assembly that are constructed in vitro or in vivo. Benefiting from the inherent advantages of peptides, such as good biocompatibility, high bioactivity, and flexible tunability, the reported PST have shown excellent application prospects in combating many major diseases including cancer, cardiovascular disease, infectious disease, autoimmune disease, metabolic disease, and so on. Through thoughtful design, the PST can be fabricated in various forms, including self‐assembled precursor molecules, functional nano‐assemblies, and macroscopic large‐scale hydrogels. The involved peptides in the PST can play different roles, such as serving drug carriers for effective delivery, acting as scaffold materials for cell culture, and functioning as bioactive sequences for treating diseases. In this review, a comprehensive overview of traditional strategies is provided to build PST and emphasize their therapeutic applications for fighting major diseases that pose a threat to human life and health. Moreover, the main challenges of PST in systems design, therapeutic application, and clinical translation are also briefly discussed. It is hoped that this review can arouse much more attention to be paid for PST and promote its practical application in the biomedical field. [ABSTRACT FROM AUTHOR]

Percutaneous vertebroplasty (PVP) is a common method used to treat Kümmell disease. In patients without neurologic symptoms, we sought to evaluate whether using the new spiral injectors instead of the traditional push-rod injectors in PVP can result in improved clinical efficacy for the treatment of Kümmell disease. A clinical retrospective study was conducted between August 2018 and December 2020. The study included patients diagnosed with single-level thoracolumbar Kümmell disease who underwent PVP surgery. The patients were divided into 2 groups: an observation group consisting of 53 patients treated with spiral injectors and a control group consisting of 68 patients treated with push-rod injectors. A 2-year follow-up period was adopted. The bone cement injection volume and occurrence of bone cement leakage were significantly greater in the observation group compared with the control group (P < 0.05). The observation group had significantly shorter operation time and intraoperative fluoroscopy times compared with the control group (P < 0.05). The scores for the visual analog scale and Oswestry Disability Index in both groups were significantly lower at 3 days or 3 months and 2 years after surgery compared with before surgery, with the scores at 2 years after surgery being significantly lower than those at 3 days or 3 months for both groups (P < 0.05). The relative anterior ledge height and Cobb angle showed significant improvement at 3 days and 2 years after surgery compared with before surgery in both groups (P < 0.05), but patients in the observation group experienced substantial improvement at 3 days and 2 years after surgery compared with those in the control group (P < 0.05). In both groups, the relative anterior ledge height was noticeably lower 2 years after surgery compared with 3 days after surgery (P < 0.05). Concurrently, there was a significant increase in the local Cobb angle over time in both groups (P < 0.05). The implementation of both spiral injectors and traditional push-rod injectors in PVP surgery yields effective pain relief, improved function, partially restored vertebral height, and corrected kyphosis in treating Kümmell disease. Compared with the push-rod injector, the spiral injector is highly efficient in restoring vertebral height, correcting kyphosis, and minimizing fluoroscopy use and operation time, but it carries a greater risk of bone cement leakage. [ABSTRACT FROM AUTHOR]

With the extensive applications of nanomaterials in drug delivery in recent years, nanocarriers with composite polymers, represented by liposomal gels, have been studied for drug delivery for numerous diseases. The drug is loaded inside the liposomal gel and is endowed with specific temperature, pH, enzyme, light, electric field and other stimulating materials; further, the release of the loaded drug is controlled by specific stimuli. Liposomal gels provide better stability for drug formulation and obtaining higher targeting and stimulus responsiveness compared to single nano-drug-loaded materials. Hence, the toxic side effects of drugs can be effectively reduced and the drug delivery efficiency, therapeutic efficacy and safety can be considerably improved. At present, research on liposome gels as drug delivery carriers is still under developing stage, and their advantages as drug carriers will be more useful in practice and become a powerful tool for human beings to cure diseases in the future. In the future studies, the synthesis and stimuli-responsive mechanism of liposomal gels can be further explored to expand their applications in the field of disease treatment and provide more innovative solutions for precision medicine and individualised therapy. This review explores the application of liposome gels with stimuli-responsiveness as drug carriers for treating diseases, the advantages of liposome gels as drug carriers, the methods and principles of their fabrication, the stimuli-responsiveness of liposome gels for targeted release against diseases and its current challenges and opportunities to suggest certain methods and ideas for the development of smarter precision-targeted hybrid nanosystems in the future. [ABSTRACT FROM AUTHOR]

Metabolic syndromes (MetS) and related cardiovascular diseases (CVDs) pose a serious threat to human health. MetS are metabolic disorders characterized by obesity, dyslipidemia, and hypertension, which increase the risk of CVDs' initiation and development. Although there are many availabile drugs for treating MetS and related CVDs, some side effects also occur. Considering the low-level side effects, many natural products have been tried to treat MetS and CVDs. A five-cyclic triterpenoid natural product, oleanolic acid (OA), has been reported to have many pharmacologic actions such as anti-hypertension, anti-hyperlipidemia, and liver protection. OA has specific advantages in the treatment of MetS and CVDs. OA achieves therapeutic effects through a variety of pathways, attracting great interest and playing a vital role in the treatment of MetS and CVDs. Consequently, in this article, we aim to review the pharmacological actions and potential mechanisms of OA in treating MetS and related CVDs. [ABSTRACT FROM AUTHOR]

Introduction: Chronic spontaneous urticaria (CSU) with autoreactivity is often resistant to antihistamines. Autologous whole blood injection (AWBI) has shown potential efficacy in the treatment of this disease, but it is controversial. It is necessary to screen patients who are suitable for this therapy in advance. This study aimed to identify biomarkers that predict the efficacy of AWBI treatment in CSU patients with autoreactivity. Methods: A total of 30 patients with autologous serum skin test-positive CSU treated with AWBI were included in this study; urticaria activity score (UAS7) was recorded and the treatment response was judged based on it. Levels of total serum IgE, anti-high-affinity IgE receptor (FcεRI) IgG, and basophils CD63 and FcεRI expressions, and D-dimer of all patients were determined and analyzed. Results: Baseline levels of total IgE, D-dimer, basophil FcεRI and CD63 expressions showed good correlations with UAS7 variations. D-dimer, basophil FcεRI and CD63 expressions changed significantly before and after AWBI treatment in AWBI responders, and the basophil FcεRI and CD63 expressions consistently and dynamically decreased in AWBI responders during the treatment. Baseline levels of total IgE, D-dimer, basophil FcεRI and CD63 expressions showed certain predictive values for AWBI response. Conclusions: Baseline levels of total IgE, D-dimer, basophil FcεRI and CD63 expressions could be biomarkers of predicting AWBI efficacy in patients with CSU with autoreactivity. [ABSTRACT FROM AUTHOR]

Background: Functional gastrointestinal disorders (FGIDs) are closely related to disorders of brain-gut interaction. FGIDs are the dominant disease of acupuncture treatment, which can improve the symptoms and emotional state. Aim: To evaluate the results and quality of the available clinical evidence and to summarize the central mechanism and effect of acupuncture on FGIDs. Methods: PubMed, EMBASE, Web of science, Cochrane Library, China National Knowledge Infrastructure (CNKI) were searched by computer to collect the randomized controlled trials (RCTs), which contained central mechanisms via fMRI research of acupuncture in the treatment of FGIDs patients. The search time limit was from the establishment of the database to June 22, 2022. Two researchers independently screened the literature, extracted data, and evaluated the quality. Results: Ten RCTs involving fMRI data were included in this study, including 4 Functional dyspepsia (FD) studies, 3 irritable bowel syndrome (IBS) studies, and 3 functional constipation (FC) studies. The score of improvements in both gastrointestinal symptoms and psychological symptoms showed that acupuncture could significantly improve the clinical symptoms of FGIDs patients, including abdominal pain, abdominal distension, frequency of defecation, and stool characteristics, and could relieve anxiety and depression symptoms of patients. Acupuncture could regulate brain functional connections and functional activity in FGIDs patients, mainly including insula, anterior cingulate cortex, prefrontal cortex, thalamus, hippocampus, amygdala and other brain regions. Conclusion: Acupuncture can improve gastrointestinal symptoms and psychological status in FGIDs patients, and regulate functional connectivity and activity of brain regions such as insula, ACC, PFC, thalamus, HIPP, amygdala, etc. These changes in brain activity may related to visceral sensation, pain regulation, emotion, but further studies of high quality are still necessary. [ABSTRACT FROM AUTHOR]

Therapeutic options for advanced prostate cancer have vastly expanded over the last decade and will continue to expand in the future. Drugs targeting the androgen receptor (AR) signaling pathway, i.e., androgen receptor targeting agents (ARTAs), remain the mainstream treatments that are increasingly transforming the disease into one that can be controlled for an extended period of time. Prostate cancer is inherently addicted to AR. Under the treatment pressure of ARTA, molecular alterations occur, leading to the clonal expansion of resistant cells in a disease state broadly categorized as castration-resistant prostate cancer (CRPC). One castration resistance mechanism involves AR splice variants (AR-Vs) lacking the ligand-binding domain. Some AR-Vs have been identified as constitutively active, capable of activating AR signaling pathways without androgenic ligands. Among these variants, AR-V7 is the most extensively studied and may be measured non-invasively using validated circulating tumor cell (CTC) tests. In the context of the evolving prostate cancer treatment landscape, novel agents are developed and evaluated for their efficacy in targeting AR-V7. In patients with metastatic CRPC (mCRPC), the availability of the AR-V7 tests will make it possible to determine whether the treatments are effective for CTC AR-V7-positive disease, even though the treatments may not be specifically designed to target AR-V7. In this review, we will first outline the current prostate cancer treatment landscape, followed by an in-depth review of relatively newer prostate cancer therapeutics, focusing on AR-targeting agents under clinical development. These drugs are categorized from the standpoint of their activities against AR-V7 through direct or indirect mechanisms. [ABSTRACT FROM AUTHOR]

Metal–organic frameworks (MOFs) have been broadly applied in biomedical and other fields. MOFs have high porosity, a large comparative area, and good biostability and have attracted significant attention, especially in cancer therapies. This paper presents the latest applications of MOFs in chemodynamic therapy (CDT), sonodynamic therapy (SDT), photodynamic therapy (PDT), photothermal therapy (PTT), immunotherapy (IT), and combination therapy for breast cancer. A combination therapy is the combination of two different treatment modalities, such as CDT and PDT combination therapy, and is considered more effective than separate therapies. Herein, we have also discussed the advantages and disadvantages of combination therapy in the treatment of breast cancer. This paper aims to illustrate the potential of MOFs in new cancer therapeutic approaches, discuss their potential advantages, and provide some reflections on the latest research results. [ABSTRACT FROM AUTHOR]

Amblyopia affects development of children's monocular vision and binocular function and becomes a largely intractable problem with increasing aging. This study is to investigate the binocular function and evaluate efficacy of digital therapy in children 8–13 years of age with anisometropic amblyopia. The patients in the digital therapy group performed the training with the digital amblyopia therapeutic software. The visual acuity and binocular function (perceptual eye position [PEP], suppression, and stereopsis) were examined at the first visit and 3-month post-treatment. Twenty-three cases in the control group and 25 cases in the digital therapy group were enrolled. The results revealed that 3-month digital therapy can effectively improve corrected distance visual acuity (CDVA) and improve the binocular function, including PEP, suppression, and second-order stereopsis in children with anisometropic amblyopia, 8–13 years of age. Digital therapy for amblyopia can effectively improve monocular CDVA of amblyopic eyes and binocular function in older children with anisometropic amblyopia. [ABSTRACT FROM AUTHOR]

The latest evidence suggested that the onset of dilated cardiomyopathy (DCM) is closely associated with immune microenvironment disturbance. Since N6‐methyladenosine (m6A) RNA methylation impacts on immunocyte function and antitumor immunity, it is predictable that m6A RNA methylation may result in immune microenvironment disorder. Here, we attempted to verify this hypothesis. We used single‐sample gene set enrichment analysis (ssGSEA) to investigate the infiltration abundance of immunocytes, single‐cell RNA‐Seq to identify key m6A regulator, and a doxorubicin (Dox)‐induced DCM mouse model to confirm our findings. ssGSEA revealed a higher infiltration abundance of CD8+ T lymphocytes, NK cells, monocytes, and B+ lymphocytes in DCM myocardium tissue. Single‐cell RNA‐Seq indicated a critical role of IGFBP2 in DCM. Cross‐checking analysis hinted an interaction between IGFBP2 and NSUN5, ALYREF, RRP8, and ALKBH3. Mechanically, IGFBP2‐mediated RNA methylation deteriorated the immune microenvironment and thus increased the risk of DCM by enhancing CD8+ T lymphocyte, NK cell, monocyte, B+ lymphocyte infiltration and activating check‐point, MHC‐I, and T cell co‐stimulation signaling pathways. In the DCM mouse model, echocardiography indicated a significant reduction in ejection fraction (EF) and fractional shortening (FS) and an increase in left ventricular internal dimensions at systole (LVIDs) and diastole (LVIDd). MASSON staining indicated an increased fibrosis in myocardium tissue. qPCR and immunofluorescence staining indicated a significant increase in mRNA and protein levels of IGFBP2. The present study indicated that IGFBP2‐mediated RNA methylation remodeled the immune microenvironment and increased the risk of DCM. IGFBP2 may serve as potential therapeutic target for DCM. [ABSTRACT FROM AUTHOR]

Drugs may undergo costly preclinical studies but still fail to demonstrate their efficacy in clinical trials, which makes it challenging to discover new drugs. Both in vitro and in vivo models are essential for disease research and therapeutic development. However, these models cannot simulate the physiological and pathological environment in the human body, resulting in limited drug detection and inaccurate disease modelling, failing to provide valid guidance for clinical application. Organs-on-chips (OCs) are devices that serve as a micro-physiological system or a tissue-on-a-chip; they provide accurate insights into certain functions and the pathophysiology of organs to precisely predict the safety and efficiency of drugs in the body. OCs are faster, more economical, and more precise. Thus, they are projected to become a crucial addition to, and a long-term replacement for, traditional preclinical cell cultures, animal studies, and even human clinical trials. This paper first outlines the nature of OCs and their significance, and then details their manufacturing-related materials and methodology. It also discusses applications of OCs in drug screening and disease modelling and treatment, and presents the future perspective of OCs. [ABSTRACT FROM AUTHOR]

There is an increasing interest in non-pharmacological treatments for children with attention-deficit/hyperactivity disorder (AD/HD), especially digital techniques that can be remotely delivered, such as neurofeedback (NFT) and computerized cognitive training (CCT). In this study, a randomized controlled design was used to compare training outcomes between remotely delivered NFT, CCT, and combined NFT/CCT training approaches. A total of 121 children with AD/HD were randomly assigned to the NFT, CCT, or NFT/CCT training groups, with 80 children completing the training program. Pre- and post-training symptoms (primary outcome), executive and daily functions were measured using questionnaires as well as resting EEG during eyes-closed (EC) and eyes-open (EO) conditions. After 3 months of training, the inattentive and hyperactive/impulsive symptoms, inhibition, working memory, learning and life skills of the three groups of children were significantly improved. The objective EEG activity showed a consistent increase in the relative alpha power in the EO condition among the three training groups. Training differences were not observed between groups. There was a positive correlation between pre-training EO relative alpha power and symptom improvement scores of inattention and hyperactivity/impulsivity, as well as a negative correlation between pre-training inattention scores and change in EO relative alpha. This study verified the training effects of NFT, CCT, and combined NFT/CCT training in children with AD/HD and revealed an objective therapeutic role for individual relative alpha activity. The verified feasibility and effectiveness of home-based digital training support promotion and application of digital remote training. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 Omicron led to the most serious outbreak of COVID-19 in Hong Kong in 2022. Under the pressure of a high volume of patients and limited medical resources, Chinese herbal medicine (CHM) has been extensively used. This is a case-control study of the infected patients that aims to evaluate the effectiveness of CHM using data extracted from the Hong Kong Baptist University Telemedicine Chinese Medicine Centre database. Patients with COVID-19 confirmed by either a rapid antigen test or a polymerase chain reaction who had completed two consultations and taken CHM within 10 days of the first positive test were included in the study (CHM group, n = 3 1 1). The matched control cases were those who did not take CHM within 10 days of the first positive test and were based on age (± 3 years), vaccine doses (< 3 doses, or 3 doses), and gender (no-CHM group, n = 3 1 1). The outcomes included the negative conversion time (NCT, primary outcome), total score of individual symptoms, number of the reported symptoms, and individual symptom disappearance rates. The NCT of the CHM group (median days: 7.0, interquartile range: 6.0–8.0) was significantly shorter than that of the no-CHM group (8.0, 7.0–10.5; P = 0. 0 1 6). CHM treatment significantly reduced the total score of individual symptoms (P < 0. 0 0 1) and the number of the reported symptoms (P < 0. 0 0 1) as compared with that of the no-CHM group. Additionally, the symptom disappearance rates of symptoms such as chills, cough, sputum, dry throat, itching throat, headache, chest tightness, abdominal pain, diarrhea, and fatigue were significantly higher in the CHM group than in the no-CHM group. In conclusion, CHM intervention can significantly reduce NCT and COVID-19 symptoms. Chinese medicine can be accurately prescribed based on a telemedical consultation. [ABSTRACT FROM AUTHOR]

Background: Keloids and hypertrophic scars frustrate patients by the deformity of appearance and organ dysfunction. Many modalities had been tried in clinic practice, but the results are unsatisfied. Objective: We retrospectively analysed the combined application of bleomycin and triamcinolone for the treatment of keloids and hypertrophic scars. Methods: The combination of bleomycin and triamcin acetonide was applied to the treatment of keloids and hypertrophic scars, 86 cases accepted the treatment. Follow‐up 2–5 years after treatment. Results: (1) The pain of scars and itching symptoms have basically subsided through treatment. (2) After drug injection treatment, the keloid began to shrink, some of the keloids disappeared. (3) Small keloids did not recur after treatment. Large keloids had local recurrence after treatment. When further treatment was given, the recurrence disappeared. Conclusion: The combined application of bleomycin and triamcin acetonide can effectively cure keloids and hypertrophic scars. [ABSTRACT FROM AUTHOR]

This cross-sectional study identified 2, 585 women aged 50–70 with certain diseases, health behaviors and psychological health problems among a representative and community-conducted sample of women in Hunan Province of China. It disclosed their poor health status: 51.0% had chronic diseases, 49.6% had gynecopathy, 23.6% had mastopathy, 57.1% failed to avoid secondhand smoke, less than 50% completed periodic health examinations, and 3.1% were anxious. Chronic diseases are expected to be serious health problems in the next 10 years, emphasizing the importance of women discussing their health status. Common diseases should be managed via public health service projects, and free screening and treatment of common diseases should be provided. To enhance women's health knowledge and awareness, targeted health education is necessary in accordance with their physiological and psychological characteristics. [ABSTRACT FROM AUTHOR]

Noncancerous diseases include a wide plethora of medical conditions beyond cancer and are a major cause of mortality around the world. Despite progresses in clinical research, many puzzles about these diseases remain unanswered, and new therapies are continuously being sought. The evolution of bio-nanomedicine has enabled huge advancements in biosensing, diagnosis, bioimaging, and therapeutics. The recent development of aggregation-induced emission luminogens (AIEgens) has provided an impetus to the field of molecular bionanomaterials. Following aggregation, AIEgens show strong emission, overcoming the problems associated with the aggregation-caused quenching (ACQ) effect. They also have other unique properties, including low background interferences, high signal-to-noise ratios, photostability, and excellent biocompatibility, along with activatable aggregation-enhanced theranostic effects, which help them achieve excellent therapeutic effects as an one-for-all multimodal theranostic platform. This review provides a comprehensive overview of the overall progresses in AIEgen-based nanoplatforms for the detection, diagnosis, bioimaging, and bioimaging-guided treatment of noncancerous diseases. In addition, it details future perspectives and the potential clinical applications of these AIEgens in noncancerous diseases are also proposed. This review hopes to motivate further interest in this topic and promote ideation for the further exploration of more advanced AIEgens in a broad range of biomedical and clinical applications in patients with noncancerous diseases. [ABSTRACT FROM AUTHOR]

Erdong Gao (EDG), consisting equally of roots of Asparagi Radix and Ophiopogonis Radix, is a well-known traditional Chinese formulation that has been used to treat cough and throat pain for centuries. However, the bioactive components in EDG remain to be elucidated. In this study, a rapid and effective method involving live cell bio-specific extraction and HPLC-Q-TOF-MS/MS was established to rapidly screen and identify the anti-inflammatory compounds of an EDG extract. One hundred and twenty-four components were identified in EDG extract using HPLC-Q-TOF-MS/MS analysis. After co-incubation with 16HBE, HPAEpiCs and HUVECs, which have been validated as the key target cells for pulmonary diseases, sixteen components were demonstrated to exhibit an affinity for binding to them. Furthermore, fifteen components were subsequently verified to exert anti-inflammatory effects on lipopolysaccharide (LPS)-induced 16HBE, HPAEpiCs and HUVECs via inhibiting the release of TNF-α and IL-6, indicating that nine steroidal saponins may possess potential for the treatment of lung-related diseases. Taken together, our study provides evidence that live cell biospecific extraction combined with the HPLC-Q-TOF-MS/MS technique was an efficient method for rapid screening potential bioactive components in traditional Chinese medicines and the structure activity relationship of steroidal saponins in EDG was summarized for the first time. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has ravaged the world for three years. Most countries have adjusted policies and strategies in response to the burden of COVID-19. The severity of COVID-19 seems to be diminishing as the case fatality rate has declined and the number of vaccinated people has increased markedly. Given the large population worldwide, we need to pay attention to the continuing COVID-19 burden. Globally, the number of cases remains at a certain level, and the number of cases is still increasing in China. We also need to deal with shortages of medical resources, antipyretics, and home nursing facilities. SARS-CoV-2 will coexist with humans for a long time, and predicting viral mutations and pandemic trends will be difficult. The reform of the whole public health system is imperative. A comprehensive surveillance system should be created to determine the proportion of various pathogens and to guard against mixed infections of respiratory infectious diseases. A comprehensive response mechanism, including preventive measures and medical treatments, should be created as soon as possible to monitor the status of the epidemic and to deal with the long-term health burden of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that gut microbiota plays critical roles in various human diseases. High-throughput technology has been widely applied to characterize the microbial ecosystems, which led to an explosion of different types of molecular profiling data, such as metagenomics, metatranscriptomics and metabolomics. For analysis of such data, machine learning algorithms have shown to be useful for identifying key molecular signatures, discovering potential patient stratifications, and particularly for generating models that can accurately predict phenotypes. In this review, we first discuss how dysbiosis of the intestinal microbiota is linked to human disease development and how potential modulation strategies of the gut microbial ecosystem can be used for disease treatment. In addition, we introduce categories and workflows of different machine learning approaches, and how they can be used to perform integrative analysis of multi-omics data. Finally, we review advances of machine learning in gut microbiome applications and discuss related challenges. Based on this we conclude that machine learning is very well suited for analysis of gut microbiome and that these approaches can be useful for development of gut microbe-targeted therapies, which ultimately can help in achieving personalized and precision medicine. [ABSTRACT FROM AUTHOR]

The liver is an important organ in the human body and performs many functions, such as digestion, detoxification, metabolism, immune responses, and vitamin and mineral storage. Therefore, disorders of liver functions triggered by various hepatic diseases, including hepatitis B virus infection, nonalcoholic steatohepatitis, hepatic fibrosis, hepatocellular carcinoma, and transplant rejection, significantly threaten human health worldwide. Polymer-based nanomedicines, which can be easily engineered with ideal physicochemical characteristics and functions, have considerable merits, including contributions to improved therapeutic outcomes and reduced adverse effects of drugs, in the treatment of hepatic diseases compared to traditional therapeutic agents. This review describes liver anatomy and function, and liver targeting strategies, hepatic disease treatment applications and intrahepatic fates of polymeric nanomedicines. The challenges and outlooks of hepatic disease treatment with polymeric nanomedicines are also discussed. [ABSTRACT FROM AUTHOR]

Yang and colleagues expounded two possible pathways contributing to pollen's effect on COVID-19 infection using a multiple-adjusted generalized additive (GAM) model.[12] Besides further recognizing the features of allergy,[13] knowing the allergen-encoding genes and their isoforms at the chromosomal level may also help us to detect novel allergens.[14] Zhao and colleagues have identified three well-recognized mango fruit allergen molecules by using combined omics tools and immunological methods. It has now been over 3 years since the coronavirus disease 2019 (COVID-19) was declared a global pandemic, and its end now appears to be in sight. The latest progress and contributions of these scholars in understanding the "epithelial barrier theory" as the gateway to allergic diseases, allergen recognition, and promising treatments are highlighted in this special "China Issue" of I Allergy i (Figure 1). [Extracted from the article]

Inhibition of the bromodomain of the CREB (cyclic-AMP response element-binding protein) binding protein (CBP) is a particularly promising new therapeutic approach for cancer. Benzimidazole derivatives CCS1477 and its analogues (8 and 9) are highly potent and selective CBP bromodomain inhibitors, with K d values of 26.4, 37.0, and 34.3 nM in ITC assay, respectively. Among these compounds, CCS1477 is undergoing phase Ib/IIa clinical trials for the treatment of various cancers. Thus, we determined the co-crystal structures of CCS1477 and its analogues in complex with CBP bromodomain and revealed the detailed binding modes. Furthermore, overlapping with other reported co-crystal structures allowed us to identify that interaction with Arg1173, LPF shelf, and ZA channel was critical for keeping strong biological activity and selectivity. Collectively, this study provided a structural basis for CBP bromodomain inhibitors design. • CCS1477 is the only CBP bromodomain inhibitor in clinical trials. • The binding mode of CCS1477 with the CBP bromodomain was revealed by X-ray crystallography. • Interaction with Arg1173 is critical for high binding affinity of CCS1477. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) is increasingly used in patients undergoing complex thoracic surgical procedures. However, studies reporting the clinical outcomes of these patients are limited to case reports, without real consensus. Our aim was to evaluate the perioperative use of ECMO as respiratory and/or circulatory support in thoracic surgery: indications, benefits, and perioperative management. Methods: Between May 2013 and December 2018, we reviewed the clinical data of 15 patients (11 males and 4 females; mean age: 47 years old; range, 25–73 years) undergoing ECMO-assisted thoracic surgery in our hospital. Results: Of the 15 patients, 10 cases received peripheral veno-arterial (VA) ECMO and five cases received veno-venous (VV) ECMO. Indications for ECMO were pulmonary transplantation with hard-to-maintain oxygenation (n = 5), traumatic main bronchial rupture (n = 2), traumatic lung injury (n = 1), airway tumor leading to severe airway stenosis (n = 2), huge thoracic mass infiltrated vena cava (n = 5). The ECMO duration was 1–51 hours. All patients were successfully extubated and weaned from ECMO postoperatively. The main complications were hemorrhage (26.7%), infection (33.3%), acute hepatic dysfunction (33.3%), and venous thrombosis (26.7%). There was only one hospital death and postoperative one-year survival rate was 86%. Conclusion: Our experience indicates that ECMO is a feasible method for complex trachea-bronchial surgery, huge thoracic mass excision and lung transplantation, and the ECMO-related risks may be justified. With further accumulation of experience with ECMO, a more sophisticated protocol for management of critical airway or heart failure problems in thoracic surgeries can be derived. [ABSTRACT FROM AUTHOR]

Sceletium tortuosum (SCT) has been utilized medicinally by indigenous Koi-San people purportedly for mood elevation. SCT extracts are reported to be neuroprotective and have efficacy in improving cognition. However, it is still unclear which of the pharmacological mechanisms of SCT contribute to the therapeutic potential for neurodegenerative disorders. Hence, this study investigated two aspects–firstly, the abilities of neuroprotective sub-fractions from SCT on scavenging radicals, inhibiting some usual targets relevant to Alzheimer's disease (AD) or Parkinson's disease (PD), and secondly utilizing the network pharmacology related methods to search probable mechanisms using Surflex-Dock program to show the key targets and corresponding SCT constituents. The results indicated sub-fractions from SCT could scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, inhibit acetylcholinesterase (AChE), monoamine oxidase type B (MAO-B) and N-methyl-D-aspartic acid receptor (NMDAR). Furthermore, the results of gene ontology and docking analyses indicated the key targets involved in the probable treatment of AD or PD might be AChE, MAO-B, NMDAR subunit2B (GluN2B-NMDAR), adenosine A2A receptor and cannabinoid receptor 2, and the corresponding constituents in Sceletium tortuosum might be N-trans-feruloyl-3-methyldopamine, dihydrojoubertiamine and other mesembrine type alkaloids. In summary, this study has provided new evidence for the therapeutic potential of SCT in the treatment of AD or PD, as well as the key targets and notable constituents in SCT. Therefore, we propose SCT could be a natural chemical resource for lead compounds in the treatment of neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels exert a critical inhibitory influence on neurons. Neuronal GIRK channels mediate the G protein-dependent, direct/postsynaptic inhibitory effect of many neurotransmitters including γ-aminobutyric acid (GABA), serotonin, dopamine, adenosine, somatostatin, and enkephalin. In addition to their complex regulation by G proteins, neuronal GIRK channel activity is sensitive to phosphatidylinositol 4,5-bisphosphate (PIP2), phosphorylation, regulator of G protein signaling (RGS) proteins, intracellular Na+ and Ca2+, and cholesterol. The application of genetic and viral manipulations in rodent models, together with recent progress in the development of GIRK channel modulators, has increased our understanding of the physiological and behavioral impact of neuronal GIRK channels. Work in rodent models has also revealed that neuronal GIRK channel activity is modified, transiently or persistently, by various stimuli including exposure drugs of abuse, changes in neuronal activity patterns, and aversive experience. A growing body of preclinical and clinical evidence suggests that dysregulation of GIRK channel activity contributes to neurological diseases and disorders. The primary goals of this review are to highlight fundamental principles of neuronal GIRK channel biology, mechanisms of GIRK channel regulation and plasticity, the nascent landscape of GIRK channel pharmacology, and the potential relevance of GIRK channels to the pathophysiology and treatment of neurological diseases and disorders. [ABSTRACT FROM AUTHOR]

Since the number of raw material selections for the synthesis of carbon dots (CDs) has grown extensively, herbal medicine as a precursor receives an increasing amount of attention. Compared with other biomass precursors, CDs derived from herbal medicine (HM-CDs) have become the most recent incomer in the family of CDs. In recent ten years, a great many studies have revealed that HM-CDs tend to be good at theranostics without drug loading. However, the relevant development and research results are not systematically reviewed. Herein, the origin and history of HM-CDs are outlined, especially their functional performances in medical diagnosis and treatment. Besides, we sort out the herbal medicine precursors, and analyze the primary synthetic methods and the key characteristics. In terms of the applications of HM-CDs, medical therapeutics, ion and molecular detection, bioimaging, as well as pH sensing are summarized. Finally, we discuss the crucial challenges and future prospects. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is a major subtype of lung cancer with a relatively poor prognosis, requiring novel therapeutic approaches. Great advances in new immunotherapy strategies have shown encouraging results in lung cancer patients. This study is aimed at elucidating the function of SLC2A5 in the prognosis and pathogenesis of LUAD by analyzing public databases. The differential expression of SLC2A5 in various tissues from Oncomine, GEPIA, and other databases was obtained, and SLC2A5 expression at the protein level in normal and tumor tissues was detected with the use of the HPA database. Then, we used the UALCAN database to analyze the expression of SLC2A5 in different clinical feature subgroups. Notably, in both PrognoScan and Kaplan-Meier plotter databases, we found a certain association between SLC2A5 and poor OS outcomes in LUAD patients. Studies based on the TIMER database show a strong correlation between SLC2A5 expression and various immune cell infiltrates and markers. The data analysis in the UALCAN database showed that the decreased promoter methylation level of SLC2A5 in LUAD may lead to the high expression of SLC2A5. Finally, we used the LinkedOmics database to evaluate the SLC2A5-related coexpression and functional networks in LUAD and to investigate their role in tumor immunity. These findings suggest that SLC2A5 correlated with immune infiltration can be used as a candidate diagnostic and prognostic biomarker in LUAD patients. [ABSTRACT FROM AUTHOR]

Objective: The lack of appropriate preclinical models of ovarian yolk sac tumor (OYST) is currently hindering the pursuit of new methods of treatment and investigation of the pathogenesis of the disease. We developed and characterized an OYST patient-derived xenograft (PDX) model in this study. Methods: Tumor fragments from a patient with an OYST were implanted subcutaneously into BALB/c Nude mice. Engrafted xenografts were compared with the original tumor according to histology, immunohistochemistry, humanized identified, and drug efficacy testing with in vivo treatment programs. Results: There was a high degree of histologic and immunohistochemical (IHC) resemblance between the established PDX model and its corresponding human tumors. Bleomycin, etoposide, and cisplatin (JEB) chemotherapy regimens were effective in clinical patients and were effective in the OYST PDX model; therefore, the effect of PDX intervention was consistent with clinical outcomes of OYSTs. Conclusion: We have successfully established an OYST PDX model. This OYST model preserves the basic molecular features of the primary human tumor, thereby providing a valuable method to preclinically evaluate new treatments and explore disease pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose: Tumor heterogeneity limits the predictive value of PD-L1 expression and influences the outcomes of the immunohistochemical assay for therapy-induced changes in PD-L1 levels. This study aimed to determine the predictive value of PD-L1 for non-small cell lung carcinoma (NSCLC), thereby developing imaging agents to non-invasively image and examine the effect of the therapeutic response to PD-L1 blockade therapy. Methods: A cohort of 102 patients with lung cancer was analyzed, and the prognostic significance of PD-L1 expression level was investigated. Recombinant human PD-1 ECD protein (rhPD1) was expressed, purified, and labeled with 64Cu for the evaluation of PD-L1 status in tumors. Mice subcutaneously bearing PD-L1 high-expressing tumor HCC827 and PD-L1 low-expressing tumor A549 were used to determine tracer-target specificity and examine the effect of therapeutic response to PD-L1 blockade therapy. Results: PD-L1 was proved to be a good prognosis marker for NSCLC, and its expression was correlated with the histology of NSCLC. PET imaging revealed high tumor accumulation of 64Cu-NOTA-rhPD1 in HCC827 tumors (9.0 ± 0.5%ID/g), whereas it was 3.2 ± 0.4%ID/g in A549 tumors at 3 h post-injection. The lower tumor uptake (3.1 ± 0.3%ID/g) of 64Cu-labeled denatured rhPD1 in HCC827 tumors at 3 h post-injection (p < 0.001) demonstrated the target specificity of 64Cu-NOTA-rhPD1. Furthermore, PET showed that 64Cu-NOTA-rhPD1 sensitively monitored treatment-related changes in PD-L1 expression, and seemed to be superior to [18F]FDG. Conclusion: We identified PD-L1 as a good prognosis marker for surgically resected NSCLC and developed the PET tracer 64Cu-NOTA-rhPD1 with high target specificity for PD-L1. [ABSTRACT FROM AUTHOR]

Selective activation of prodrugs is an important approach to reduce the side effects of disease treatment. We report a prodrug design concept for metal complexes, termed "metal‐carrying prochelator", which can co‐carry a metal ion and chelator within a single small‐molecule compound and remain inert until it undergoes a specifically triggered intramolecular chelation to synthesize a bioactive metal complex in situ for targeted therapy. As a proof‐of‐concept, we designed a H2O2‐responsive small‐molecule prochelator, DPBD, based on the strong chelator diethyldithiocarbamate (DTC) and copper. DPBD can carry Cu2+ (DPBD‐Cu) and respond to elevated H2O2 levels in tumor cells by releasing DTC, which rapidly chelates Cu2+ from DPBD‐Cu affording a DTC–copper complex with high cytotoxicity, realizing potent antitumor efficacy with low systemic toxicity. Thus, with its unique intramolecularly triggered activation mechanism, this concept based on a small‐molecule metal‐carrying prochelator can help in the prodrug design of metal complexes. [ABSTRACT FROM AUTHOR]

Selective activation of prodrugs is an important approach to reduce the side effects of disease treatment. We report a prodrug design concept for metal complexes, termed "metal‐carrying prochelator", which can co‐carry a metal ion and chelator within a single small‐molecule compound and remain inert until it undergoes a specifically triggered intramolecular chelation to synthesize a bioactive metal complex in situ for targeted therapy. As a proof‐of‐concept, we designed a H2O2‐responsive small‐molecule prochelator, DPBD, based on the strong chelator diethyldithiocarbamate (DTC) and copper. DPBD can carry Cu2+ (DPBD‐Cu) and respond to elevated H2O2 levels in tumor cells by releasing DTC, which rapidly chelates Cu2+ from DPBD‐Cu affording a DTC–copper complex with high cytotoxicity, realizing potent antitumor efficacy with low systemic toxicity. Thus, with its unique intramolecularly triggered activation mechanism, this concept based on a small‐molecule metal‐carrying prochelator can help in the prodrug design of metal complexes. [ABSTRACT FROM AUTHOR]

Testing the Common-Sense Model, this random telephone survey examined the associations between illness representations of COVID-19 and behavioral intention to visit hospitals for scheduled medical consultations (BI-VHSMC), and the mediations via coping and fear of nosocomial infection among 300 Chinese adults. The prevalence of BI-VHSMC was 62.3%. Mediation analysis found that maladaptive coping (rumination and catastrophizing) and fear of nosocomial infection mediated the associations between various dimensions of illness representations of COVID-19 (e.g. consequence and controllability) and BI-VHSMC, both indirectly and serially. Illness representations, coping, and fear should be considered when planning related health promotion during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

The stimuli‐responsiveness of injectable hydrogel has been drastically developed for the controlled release of drugs and has achieved encouraging curative effects in a variety of diseases including wounds, cardiovascular diseases, and tumors. The gelation, swelling, and degradation of such hydrogels respond to endogenous biochemical factors (such as pH, reactive oxygen species, glutathione, enzymes, glucose) and/or to exogenous physical stimulations (like light, magnetism, electricity, and ultrasound), thereby accurately releasing loaded drugs in response to specifically pathological status and as desired for treatment plan, and thus improving therapeutic efficacy effectively. This paper gives a detailed introduction of recent progresses in responsive injectable hydrogels and focuses on the design strategy of various stimuli‐sensitivities and their resultant alteration of gel dissociation and drug liberation behavior. Their application in disease treatment is also discussed. [ABSTRACT FROM AUTHOR]

Introduction. Uterine subinvolution, especially the subinvolution of the placental site, can be a life-threatening disease that induces secondary postpartum hemorrhage (PPH). Chinese Herbal Medicine has been widely used to improve postpartum recovery and treat uterine subinvolution for thousands of years. Yet, there are many potential laws hidden that are worth exploring. Methods. Prescriptions treating uterine subinvolution were searched and collected to form datasets. Data mining methods including frequency analysis, cluster analysis, and association rule learning were performed to uncover the potent prescription laws of uterine subinvolution treatment. Results. A total of 803 formulae involving 249 herbs were obtained. The top 6 most frequently used herbs were Angelicae Sinensis Radix (Danggui), Chuanxiong Rhizoma (Chuanxiong), Leonuri Herba (Yimucao), Persicae Semen (Taoren), Zingiberis Rhizoma Preparatum (Paojiang), and Radix Glycyrrhizae Preparata (Zhigancao). Most of the 249 herbs were being warm in properties, sweet in tastes, and mainly distributed to liver and spleen meridian tropisms. Deficiency-tonifying herbs accounted for the most proportion and heat-clearing herbs ranked the second, followed by blood-activating and stasis-eliminating herbs. 6 clusters were generated by hierarchical clustering, and 5 of them were of clinical significance. 78 rules with support values over 0.25, confidence values over 0.8, and lift values greater than 1 were generated by association rule learning. Conclusion. The basic principles for uterine subinvolution treatment were deficiency-tonifying, heat-clearing, blood-activating, and stasis-eliminating. Herbs with warm properties, sweet tastes, and liver and spleen meridian tropisms are generally suitable. In addition, Sheng-Hua-Tang was the most frequently used formula for the treatment of uterine subinvolution, yet the dialectical prescriptions were diversified with different patterns/symptoms. [ABSTRACT FROM AUTHOR]

Objective. Shenling Baizhu San (SLBZS) is reported as an effective drug for ulcerative colitis (UC); however, its effect on intestinal flora remains unknown. In this study, we investigated the effect of SLBZS on intestinal flora in a rat model of UC with spleen deficiency and dampness. Methods. UC was induced in rats using 2,4,6-trinitrobenzene sulfonic acid on the basis of a model of spleen deficiency and dampness. The 16S rDNA sequencing was used to detect structural changes in the intestinal flora; the phylogenetic investigation of communities by reconstruction of unobserved state (PICRUSt) analysis was used to predict the altered pathways. Results. Compared with the model group, rats in the SLBZS group exhibited decreased levels of TNF-α P < 0.05 , and increased abundance and diversity of the intestinal flora. The abundance of Actinobacteria P < 0.001 and Bacteroides P < 0.01 increased and that of Firmicutes decreased P < 0.001 , and the abundance of Bifidobacterium P < 0.05 and Allobaculum increased. PICRUSt analysis showed that the altered pathways between the groups were those of fatty acid and antibiotic biosynthesis, amino acid metabolism, and the pentose phosphate pathway. Conclusions. SLBZS can regulate the structure and function of the intestinal flora, alter expression levels of certain metabolic pathways, and has the potential to treat UC. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have become a promising tool for neurorestorative therapy of neurodegenerative diseases (NDDs), which are mainly characterized by the progressive and irreversible loss of neuronal structure and function in the central or peripheral nervous system. Recently, studies have reported that genetic manipulation mediated by noncoding RNAs (ncRNAs) can increase survival and neural regeneration of transplanted MSCs, offering a new strategy for clinical translation. In this review, we summarize the potential role and regulatory mechanism of two major types of ncRNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), during the neurogenesis of MSCs with gene expression profile analyses. We also overview the realization of MSC-based therapy mediated by ncRNAs in the treatment of spinal cord injury, stroke, Alzheimer's disease and peripheral nerve injury. It is expected that ncRNAs will become promising therapeutic targets for NDD on stem cells, while the underlying mechanisms require further exploration. [ABSTRACT FROM AUTHOR]

Inter-organ communication through hormones, cytokines and extracellular vesicles (EVs) has emerged to contribute to the physiological states and pathological processes of the human body. Notably, the liver coordinates multiple tissues and organs to maintain homeostasis and maximize energy utilization, with the underlying mechanisms being unraveled in recent studies. Particularly, liver-derived EVs have been found to play a key role in regulating health and disease. As an endocrine organ, the liver has also been found to perform functions via the secretion of hepatokines. Investigating the multi-organ communication centered on the liver, especially in the manner of EVs and hepatokines, is of great importance to the diagnosis and treatment of liver-related diseases. This review summarizes the crosstalk between the liver and distant organs, including the brain, the bone, the adipose tissue and the intestine in noticeable situations. The discussion of these contents will add to a new dimension of organismal homeostasis and shed light on novel theranostics of pathologies. [Display omitted] [ABSTRACT FROM AUTHOR]

Although the Traditional Chinese Medicine (TCM) prescription of Danggui Shaoyao San (DSS) presents substantial clinical efficacy and promising clinical prospects, the safety of DSS and its extracts have been inadequately investigated. The larva-adult duality of the zebrafish model offers a more efficient approach for evaluating the safety of herbal preparations in the fields of toxicology and pharmacology. To investigate the acute toxicity of the extract derived from Danggui Shaoyao San, a traditional Chinese medicine preparation, on both Danio rerio embryos and adult organisms. The components of DSS were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The hatching rate of Danio rerio juveniles with different concentrations of DSS was calculated and the morphological changes of juveniles after administration were observed through a microscope. The behavioral trajectory of the adult fish was recorded by the observation tower of the automated Danio rerio analysis system, and DSS's effects on the behavior was analyzed. The pathological changes of Danio rerio gills, livers, kidneys, intestines and spermaries were examined using HE staining. Compared with the control group, 25, 50 and 100 mg/L of DSS did not elicit any significant impacts on the hatching rate and morphology. Both 200 mg/L and the propylene glycol 2% reduced the hatching rate and caused the morphological teratogenic changes of the juvenile fish. The dosage of DSS below 100 mg/L had no discernible effect on the behavior of the adult fish, whereas the application of propylene glycol 2% was found to stimulate the adult fish, resulting in a notable increase in high-speed movement distance. 100 mg/L DSS group was not observed to cause any noticeable damage to the gills, livers, intestines and spermaries of Danio rerio , only mild nephrotoxicity was detected. The propylene glycol 2% group was found to result in pathological changes such as hyperplasia of epithelial cells on secondary lamellae, liver cell outline loss or atypia, tubal disorganization, goblet cell hypertrophy and irregularly arranged spermatozoa. A viable approach for conducting toxicological studies on TCM preparations was developed and tested in this research. The findings showed that Danggui Shaoyao San has minimal acute toxicity to embryos and adult organisms at concentrations up to 100 mg/L. These results indicate that Danggui Shaoyao San is a safe TCM preparation. [Display omitted] • A study explored acute toxicity of Danggui Shaoyao San (DSS), a TCM preparation, using larva-adult zebrafish model. • Liquid chromatography-tandem mass spectrometry identified DSS components. • Hatching rate, juvenile morphology, adult fish behavior, and HE staining for pathology were assessed. • Results showed minimal acute toxicity up to 100 mg/L, affirming DSS as a safe TCM preparation. • Larva-adult zebrafish model enhances efficiency herbal preparation safety evaluation in toxicology and pharmacology. [ABSTRACT FROM AUTHOR]

Numerous studies have confirmed the great application potentials of small extracellular vesicles (sEVs) in biological medical field, especially in tissue repair and regeneration. However, the production capability of sEVs by noncancerous cells is very limited, while their dosage requirements in disease treatments are usually very high. Meanwhile, as cell aging, the sEV production capability of cells decreases and the biological function of sEVs changes accordingly. In addition, for special applications, sEVs carrying desired bioactive substances should be designed to perform their expected biological function. Therefore, improving the production of sEVs and precisely regulating their biological function are of great significance for promoting the clinical applications of sEVs. In this review, some of the current classic strategies in affecting the cellular behaviors of donor cells and subsequently regulating the production and biological function of their sEVs are summarized, including gene engineering methods, stress-inducing conditions, chemical regulators, physical methods, and biomaterial stimulations. Through applying these strategies, increased yield of sEVs with required biological function can be obtained for disease treatment and tissue repair, such as bone regeneration, wound healing, nerve function recovery and cancer treatment, which could not only reduce the harvest cost of sEV but promote the practical applications of sEVs in clinic. [ABSTRACT FROM AUTHOR]

Bacteria-induced acute lung infection (ALI) is a severe burden to human health, which could cause acute respiratory distress syndrome (ARDS) and kill the patient rapidly. Therefore, it is of great significance to develop effective nanomedicine and therapeutic approach to eliminate the invading bacteria in the lung and manage ALI. In this study, we design a layer-by-layer (LbL) liposome-polymer hybrid nanoparticle (HNP) with a pH-triggered drug release profile to deliver antibiotics for the eradication of bacteria to treat ALI. The liposome is prepared by the lipid film hydration method with a homogenous hydrodynamic diameter and low polydispersity index (PDI). The antibiotic spectinomycin is efficiently loaded into the liposomal core through the pH-gradient method. The pH-sensitive polycationic polymer poly(bamino ester) (PBAE) and polyanionic sodium alginate (NaAIg) layers are decorated on the surface of liposome in sequence via electrostatic interaction, resulting in spectinomycin-loaded layer-by-layer hybrid nanoparticles (denoted as Spe@HNPs) which have reasonable particle size, high stability, prolonged circulation time, and pH-triggered drug release profile. The in vitro results demonstrate that Spe@HNPs can efficiently induce the death of bacteria with low minimum inhibitory concentration (MIC) against Staphylococcus aureus (S. aureus) and drug-resistant MRSA BAA40 strains. The in vivo results reveal that Spe@HNPs can eradicate the invading MRSA BAA40 with improved antimicrobial efficacy and low sideeffect for ALI treatment. This study not only reports a promising nanomedicine but also provides an effective method to prepare nanoplatforms for drug delivery and controlled release. [ABSTRACT FROM AUTHOR]

Background. The Chinese herbal formula Mamiran cream (MMC) has been known for its ameliorative effects on diverse skin diseases, such as eczema. Atopic dermatitis (AD; eczema) is a chronic recurrent skin disease dominated by T-helper type 2-driven inflammation (Th2). Objective. In this study, the inhibitory effect of MMC on AD was investigated in vivo. Methods. An animal model was established by sensitization with 2,4-dinitrochlorobenzene (DNCB) on the skin of SD rats. Cutaneous administration of MMC was applied, and its mechanism of action was investigated via RT-PCR and IHC assay. Result. Our data showed that topical application of MMC reduced the skin severity scores and alleviated the histological changes. Furthermore, immunohistochemical analysis demonstrated that MMC significantly decreased the levels of Th2 cytokine IL-5 and IL-4Ra in the skin lesion. In addition, it was demonstrated that MMC downregulated the mRNA expression of TNF-α, IL-1β, IL-6, IL-10, and TLR4. Moreover, MMC inhibited the activation of NF-κB, JNK1, and STAT6 pathways in skin lesions. Conclusions. Our findings suggest that MMC exhibits the inhibitory effect on AD, suggesting that MMC may be a potential therapeutic agent for this atopic disorder. [ABSTRACT FROM AUTHOR]

Vitiligo is a depigmented disease featured as diagnosis simplicity and cure difficulty. Its occurrence and development are associated with a variety of factors, including oxidative stress, heredity and immunity, etc. Existing drugs for the treatment of vitiligo are to reduce the death of melanocytes and induce pigment accumulation as the main treatment strategy. Ermanin, a member of the flavonoids, is extracted from bee glue which is wildly used to treat vitiligo in traditional Chinese medicine. Therefore, this article discusses the relationship between melanogenesis and glutathione redox homeostasis by ermanin via biochemical and free radical approaches in vivo and in vitr o. In this study, we found that ermanin effectively increased the melanin content at the in vivo model (zebrafish). Moreover, the melanin levels at the in vitro models (B16F10 cells and primary melanocytes) were also increased significantly accompanied with a shift of glutathione redox homeostasis towards oxidation. Ermanin also significantly enhanced the activity of tyrosinase. Meanwhile, ermanin increased the expression levels of TYR, TRP-1, and DCT genes, while ROS accumulation and glutathione depletion mediated the accumulation of pigments caused by ermanin, which increased the production of pigments and regulated the expression mRNA levels of TYR and DCT genes. From the perspective of pigment production regulation pathways, western blot showed that the pigment accumulation caused by ermanin was closely related to the CREB-MITF pathways, it activated CREB, TYR, TRP-1, and DCT proteins. The use of CREB specific inhibitor 666-15 and MITF inhibitor ML329 confirmed that the pigment accumulation caused by ermanin was positively correlated with CREB and MITF proteins. Our findings revealed the potential mechanisms by which ermanin promoted the production of melanin through activated CREB-MITF signaling pathway and glutathione redox homeostasis towards oxidation function as a signal are beneficial to melanin production and will help develop novel therapeutic approaches for vitiligo. [Display omitted] [ABSTRACT FROM AUTHOR]

Parkinson's disease is a common neurodegenerative disorder in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alterations in the gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the CNS, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries about alterations to the gut microbiota in Parkinson's disease and focus on current mechanistic insights into the microbiota-gut-brain axis in disease pathophysiology. Moreover, we discuss the interactions between the production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we draw attention to diet modification, the use of probiotics and prebiotics and faecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease. [ABSTRACT FROM AUTHOR]

BACKGROUNDThe anti-programmed cell death 1 (anti-PD-1) antibody pembrolizumab is clinically active against non-small cell lung cancer (NSCLC). In addition to T cells, human natural killer (NK) cells, reported to have the potential to prolong the survival of patients with advanced NSCLC, also express PD-1. This study aimed to investigate the safety and efficacy of pembrolizumab plus allogeneic NK cells in patients with previously treated advanced NSCLC.METHODSIn total, 109 enrolled patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1% or higher were randomly allocated to group A (n = 55 patients given pembrolizumab plus NK cells) or group B (n = 54 patients given pembrolizumab alone). The patients received i.v. pembrolizumab (10 mg/kg) once every 3 weeks and continued treatment until the occurrence of tumor progression or unacceptable toxicity. The patients in group A continuously received 2 cycles of NK cell therapy as 1 course of treatment.RESULTSIn our study, patients in group A had longer survival than did patients in group B (median overall survival [OS]: 15.5 months vs. 13.3 months; median progression-free survival [PFS]: 6.5 months vs. 4.3 months; P < 0.05). In group A patients with a TPS of 50% or higher, the median OS and PFS was significantly longer. Moreover, the patients in group A treated with multiple courses of NK cell infusion had better OS (18.5 months) than did those who received a single course of NK cell infusion (13.5 months).CONCLUSIONPembrolizumab plus NK cell therapy yielded improved survival benefits in patients with previously treated PD-L1+ advanced NSCLC.TRIAL REGISTRATIONClinicalTrials.gov NCT02843204.FUNDINGThis work was supported by grants from the National Natural Science Foundation of China (NSFC) - Guangdong Joint Foundation of China (no. U1601225); the NSFC (no. 81671965); the Guangdong Provincial Key Laboratory Construction Project of China (no. 2017B030314034); and the Key Scientific and Technological Program of Guangzhou City (no. 201607020016). [ABSTRACT FROM AUTHOR]

Background and Purpose: Immunosuppressive drugs have shown great promise in treating autoimmune diseases in recent years. A series of novel oxazole derivatives were screened for their immunosuppressive activity. PO-322 [1H-indole-2,3-dione 3-(1,3-benzoxazol-2-ylhydrazone)] was identified as the most effective of these compounds. Here, we have investigated the mechanism(s) underlying the inhibition of T-cell proliferation in vitro by PO-322, as well as its effects on the delayed-type hypersensitivity (DTH) response and imiquimod-induced dermatitis in vivo.Experimental Approach: T-cell proliferation and apoptosis were analysed with flow cytometry. Cell viability was assessed with a CCK-8 assay. Protein kinase activity was assessed by SelectScreen Kinase Profiling Services. The phosphorylation of signal-regulated molecules was measured by Western blot. Cytokine levels were determined by elisa. The effect of PO-322 on DTH and imiquimod-induced dermatitis was evaluated in BALB/c mice.Key Results: PO-322 inhibited human T-cell proliferation with anti-CD3/anti-CD28 mAbs or alloantigen without significant cytotoxicity. Importantly, PO-322 was a selective inhibitor of the serum- and glucocorticoid-regulated kinase 1 (SGK1) and decreased NDRG1 phosphorylation but not p70S6K, STAT5, Akt, or ERK1/2 phosphorylation. Furthermore, PO-322 inhibited IFN-γ, IL-6, and IL-17 expression but not IL-10 expression. Finally, treatment with PO-322 was safe and effective for ameliorating the DTH response and imiquimod-induced dermatitis in mice.Conclusions and Implications: PO-322 exerted immunosuppressive activity in vitro and in vivo by selectively inhibiting SGK1 activity. PO-322 represents a potential lead compound for the design and development of new drugs for the treatment of autoimmune diseases. [ABSTRACT FROM AUTHOR]

The spleen, body's largest secondary lymphoid organ, is also a vital hematopoietic and immunological organ. It is regarded as one of the most significant organs in humans. As more researchers recognize the functions of the spleen, clinical methods for treating splenic diseases and spleen-targeted drug delivery systems to improve the efficacy of spleen-related therapies have gradually developed. Many modification strategies (size, charge, ligand, protein corona) and hitchhiking strategies (erythrocytes, neutrophils) of nanoparticles (NPs) have shown a significant increase in spleen targeting efficiency. However, most of the targeted drug therapy strategies for the spleen are to enhance or inhibit the immune function of the spleen to achieve therapeutic effects, and there are few studies on spleen-related diseases. In this review, we not only provide a detailed summary of the design rules for spleen-targeted drug delivery systems in recent years, but also introduce common spleen diseases (splenic tumors, splenic injuries, and splenomegaly) with the hopes of generating more ideas for future spleen research. The spleen consists of red pulp (RP), white pulp (WP), and marginal zone (MZ), and the anatomical structures of human and mouse spleen are different in the MZ, with bridging channels (BC) in the MZ of mouse. Spleen-targeted NPs can be modified in terms of size, charge, ligand, and protein corona, and the drug delivery system of erythrocyte and neutrophil hitchhiking also exists in spleen-targeted with significant delivery effects. Currently, there are two ways for a spleen-targeted drug delivery system to regulate the immune response of the spleen: on the one hand, to stimulate the spleen to produce more immune cells by enhancing the immune response, to kill the tumor cells and resist the growth of tumors, the indications of which include breast cancer, melanoma, and rectal cancer; on the other hand, to slow down the systemic or acute inflammatory diseases in the body by suppressing the immune response, such as rheumatoid arthritis. Currently, the development of medications that specifically target the spleen primarily relies on leveraging the immune capabilities of the spleen to treat disorders that are not directly related to the spleen. This is achieved by either increasing or suppressing the immune function of the spleen. Common splenic diseases include splenic tumors, splenic injury and splenomegaly. The figure was created with BioRender.com. [Display omitted] • Structure and function of the spleen contribute to targeted delivery • Strategies for designing spleen-targeted nanoparticles • Causes, signs and treatments of spleen-related diseases [ABSTRACT FROM AUTHOR]

Mepolizumab for chronic rhinosinusitis with nasal polyps: treatment efficacy by comorbidity and blood eosinophil count. Knowledge gaps in using type 2 biologics for real-world treatment of chronic rhinosinusitis with nasal polyps By translating scientific results into an integrated care strategy, biologics targeting T2 inflammation have achieved major progress in treating severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) during the last decade. In RCTs, discontinuation of biologics caused a slow bounce of nasal polyp scores and nasal symptoms, indicating that continued treatment is necessary to sustain positive outcomes. [Extracted from the article]

Aim: Mitophagy is the regulated process that targets damaged or dysfunctional mitochondria for lysosomal-mediated removal. This process is an essential element of mitochondrial quality control, and dysregulation of mitophagy may contribute to a host of diseases, most notably neurodegenerative conditions such as Parkinson's disease. Mitochondria targeted for mitophagic destruction are molecularly marked by the ubiquitination of several outer mitochondrial membrane (OMM) proteins. This ubiquitination is positively regulated, in part, by the mitochondrial-targeted kinase PINK1 and the E3 ubiquitin ligase Parkin. In contrast, the reverse phenomenon, deubiquitination, removes ubiquitin from Parkin substrates embedded in the OMM proteins, antagonizing mitophagy. Recent evidence suggests that the mitochondrial deubiquitinase USP30 negatively regulates Parkin-mediated mitophagy, providing opportunities to identify USP30 inhibitors and test for their effects in augmenting mitophagy. Here we will characterize a USP30 inhibitor and demonstrate how the pharmacological inhibition of USP30 can augment stress-induced mitophagic flux. Methods: We have conducted mitophagy and mitochondrial analyses in cultured cells. We have determined the plasma pharmacokinetics of the USP30 inhibitor in mice and conducted analyses using the mt-Keima mice to measure in vivo mitophagy directly. Results: The compound has minimal mitochondrial toxicity in cultured cells and is tolerated well in mice. Interestingly, we demonstrated tissue-specific induction of mitophagy following USP30 pharmacological inhibition. In particular, pharmacological inhibition of USP30 induces a significant increase in cardiac mitophagy without detriment to cardiac function. Conclusion: Our data support the evidence that USP30 inhibition may serve as a specific strategy to selectively increase mitophagic flux, allowing for the development of novel therapeutic approaches. [ABSTRACT FROM AUTHOR]