The quality of life of patients with chronic obstructive pulmonary disease: a bibliometric analysis.

Background: The quality of life (QOL) of patients with chronic obstructive pulmonary disease (COPD) is garnering increasing attention. However, faced with thousands of relevant clinical literature, it is becoming increasingly difficult for researchers and institutions to identify impactful research. Bibliometrics can help researchers quickly and methodically analyze the impact and hot trends of clinical research, strengthen teamwork, and solve related challenges. Therefore, we used bibliometrics to analyze and visualize data on the QOL of patients with COPD over the past 31 years to understand the key authors, research areas, and future trends. Methods: We searched the Web of Science Core Collection for literature published since the establishment of the database. The main subject terms used were "chronic obstructive pulmonary disease", "quality of life" and their different combinations. Articles were selected and exported in plain text format along with citation information. Bibliometric analysis and data visualization were performed using the R package "bibliometrix" and by incorporating statistical indicators such as the number of publications, citations and outputs of core authors, author collaborations, major journals, major research countries and collaborations, and key research themes. Results: The bibliometric analysis included 9,219 articles. Document type is unlimited. All publications were published between 1992 and 2022, and the number of published articles increased consistently each year over the past decade, with periodic fluctuations. The European Respiratory Journal and the International Journal of Chronic Obstructive Pulmonary Disease emerged as the most frequently cited journals within this domain. Key authors contributing to this field include Wedzicha JA, Jones PW, Singh D, Holland AE, and Wouters EFM. The United States and the United Kingdom exhibited a high volume of publications, high citation rates, and relatively intense international collaboration in related areas, followed by China, Spain, Canada, and Australia in these metrics. Notably, prominent topics within this field included emphysema, pulmonary rehabilitation, dyspnea, acute exacerbation, living status, and mortality, among others. Future research in this field will focus on microorganisms, particulate matter, family rehabilitation, and Tai Chi. Conclusions: This bibliometric analysis highlights the growing importance of QOL research in the field of COPD, which can inform clinicians, researchers, and policymakers to prioritize areas for future investigation in order to develop comprehensive, patient-centered strategies. At the same time, it is suggested that researchers should pay more attention to the core authors, strengthen international collaboration and team exchanges, actively explore characteristic clinical featured treatment measures such as Tai Chi and family rehabilitation, carry out clinical research on the integration of traditional Chinese and Western medicine and self-management, focus more on the QOL, mental health and economic and social burden of patients, and ultimately enhance the well-being of individuals with chronic respiratory diseases.

A liquid crystal in situ gel based on rotigotine for the treatment of Parkinson's disease.

One of the most common neurodegenerative illnesses is Parkinson's disease (PD). Rotigotine (RTG) is a dopamine agonist that exerts anti-Parkinsonian effects through dopamine receptor agonism to improve motor symptoms and overall performance in PD patients. In this study, an in situ liquid crystal gel called rotigotine-gel (RTG-gel) was developed using soya phosphatidyl choline (SPC) and glycerol dioleate (GDO) to provide long-acting slow-release benefits of rotigotine while minimizing side effects. This study prepared the RTG-gel precursor solution using SPC, GDO, and ethanol (in the ratio of 54:36:10, w/w/w). The internal structures of the gel were confirmed by crossed-polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), and differential scanning calorimetry (DSC). The rheological properties of the RTG-gel precursor solution indicate a favorable combination of low viscosity and excellent flowability. The gel that produced during water absorption was also highly viscous and structurally stable, which helped to maintain the drug delayed release at the injection site. In vitro release assays showed that the in vitro release of RTG-gel followed Ritger-Peppas. The RTG-gel precursor solution was administered by subcutaneous injection, and the results of in vivo pharmacokinetic tests in SD rats showed that the plasma elimination half-life (t1/2) was 59.28 ± 16.08 h; the time to peak blood concentration (Tmax) was 12.00 ± 10.32 h, and the peak concentration (Cmax) was 29.9 ± 10.10 ng/mL. The blood concentration remained above 0.1 ng/mL for 20 days after administration and was still detectable after 31 days of administration, and the bioavailability of RTG can reach 72.59%. The results of in vitro solvent exchange tests showed that the RTG-gel precursor solution undergoes rapid exchange upon contact with PBS, and the diffusion of ethanol can reach 48.1% within 60 min and 80% within 8 h. The results of cytotoxicity test showed 89.27 ± 4.32% cell survival after administration of the drug using RTG-gel. The results of tissue extraction at the administration site showed that healing of the injection site without redness and hemorrhage could be observed after 14 days of injection. The results of tissue section of the administered site showed that the inflammatory cells decreased and granulation tissue appeared after 14 days of administration, and there was basically no inflammatory cell infiltration after 35 days of administration, and the inflammatory reaction was basically eliminated. It shows that RTG-gel has some irritation to the injection site, but it can be recovered by itself in the later stage, and it has good biocompatibility. In summary, RTG-gel might be a potential RTG extended-release formulation for treating PD.

Properties of Poly (Lactic-co-Glycolic Acid) and Progress of Poly (Lactic-co-Glycolic Acid)-Based Biodegradable Materials in Biomedical Research.

In recent years, biodegradable polymers have gained the attention of many researchers for their promising applications, especially in drug delivery, due to their good biocompatibility and designable degradation time. Poly (lactic-co-glycolic acid) (PLGA) is a biodegradable functional polymer made from the polymerization of lactic acid (LA) and glycolic acid (GA) and is widely used in pharmaceuticals and medical engineering materials because of its biocompatibility, non-toxicity, and good plasticity. The aim of this review is to illustrate the progress of research on PLGA in biomedical applications, as well as its shortcomings, to provide some assistance for its future research development.

Population-Based Study of the Clinical Characteristics and Risk Factors of Ischemic Colitis.

BACKGROUND: Ischemic colitis (IC) is a common ischemic disorder of the colon caused by insufficient blood supply to the colonic mucosa. This study aimed to identify the clinical characteristics, comorbidities, and risk factors in patients with IC. METHODS: We performed a retrospective population-based study using electron video-colonoscopy imaging and pathological biopsies from 168 patients diagnosed with IC. A retrospective controlled study was used to analyze differences between a young to middle-aged patient group (78 cases) and an elderly patient group (90 cases) on the basis of clinical characteristics and risk factors. RESULTS: The primary symptoms in the 168 patients with IC were abdominal pain, diarrhea, and hematochezia. White blood cells (WBC), neutrophilic granulocyte percentage (NEUT%), C-reactive protein (CRP), and D-dimer were significantly elevated in elderly patients. The sigmoid colon and descending colon were the most common lesion locations (57.1% and 33.9%, respectively). Hypertension, cerebral infarction, and coronary heart disease were the most common comorbidities in elderly patients, while smoking history was the most common risk factor in young to middle-aged patients. CONCLUSION: The sigmoid colon and descending colon are the most affected locations in IC. Hypertension, diabetes mellitus, and cerebral infarction are the most common risk factors and comorbidities.

Prediction and follow-up of risk factors for severe SARS-CoV-2 pneumonia and application of CT visual scoring.

BACKGROUND: The SARS-CoV-2 pneumonia infection is associated with high rates of hospitalization and mortality and this has placed healthcare systems under strain. Our study provides a novel method for the progress prediction, clinical treatment and prognosis of NCP, and has important clinical value for timely treatment of severe NCP patients. OBJECTIVE: To summarize the clinical features and severe illness risk factors of the patients with novel coronavirus pneumonia (NCP), in order to provide support for the progression prediction, clinical treatment and prognosis of NCP patients. MATERIALS AND METHODS: A total of 196 NCP patients treated in our hospital from January 25, 2020 to June 21, 2020 were divided into the severe group and the mild group. The clinical features of the two groups were analyzed and compared. The risk factors were explored by using multivariate logistic regression, and the receiver operating characteristic (ROC) curve was obtained. The correlations of the risk factors with the prognosis of NCP were investigated combined with the lung function test. RESULTS: The primary clinical symptoms of 196 cases of NCP included fever in 167 cases (85.2%) and cough in 121 cases (61.73%). The chest computed tomography (CT) scans of the 178 cases (90.81%) showed a typical ground-glass opacification. In 149 cases, the lymphocyte count was decreased, while the levels of creatine kinase (CK), lactate dehydrogenase (LDH), c-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and D-dimer (D-D) increased. 44 cases (22.45%) were found to be severely ill. The multivariate logistic regression analysis demonstrated that age, underlying disease, length of hospital stay, body mass index (BMI), LDH, chest CT visual score, absolute lymphocyte count (ALC) and CRP were risk factors for severe.

Chest CT imaging characteristics of COVID-19 pneumonia in preschool children: a retrospective study.

BACKGROUND: Recently, the World Health Organization has declared the coronavirus disease 2019 (COVID-19) outbreak a public health emergency of international concern. So far, however, limited data are available for children. Therefore, we aimed to investigate the clinical and chest CT imaging characteristics of COVID-19 in preschool children. METHODS: From January 26, 2020 to February 20, 2020, the clinical and initial chest CT imaging data of eight preschool children with laboratory-confirmed COVID-19 from two hospitals were retrospectively collected. The chest CT imaging characteristics, including the distribution, shape, and density of lesions, and the pleural effusion, pleural changes, and enlarged lymph nodes were evaluated. RESULTS: Two cases (25%) were classified as mild type, and they showed no obvious abnormal CT findings or minimal pleural thickening on the right side. Five cases (62.5%) were classified as moderate type. Among these patients, one case showed consolidation located in the subpleural region of the right upper lobe, with thickening in the adjacent pleura; one case showed multiple consolidation and ground-glass opacities with blurry margins; one case displayed bronchial pneumonia-like changes in the left upper lobe; and two cases displayed asthmatic bronchitis-like changes. One case (12.5%) was classified as critical type and showed bronchial pneumonia-like changes in the bilateral lungs, presenting blurred and messy bilateral lung markings and multiple patchy shadows scattered along the lung markings with blurry margins. CONCLUSIONS: The chest CT findings of COVID-19 in preschool children are atypical and various. Accurate diagnosis requires a comprehensive evaluation of epidemiological, clinical, laboratory and CT imaging data.

Inhibition of Lung Cancer by 2-Methoxy-6-Acetyl-7-Methyljuglone Through Induction of Necroptosis by Targeting Receptor-Interacting Protein 1.

Aims: Most chemotherapeutic agents exploit apoptotic signaling to trigger cancer cell death, which frequently results in drug resistance. Necroptosis, a nonapoptotic form of regulated cell death, offers an alternative strategy to eradicate apoptosis-resistant cancer cells. We previously reported a natural necroptosis inducer 2-methoxy-6-acetyl-7-methyljuglone (MAM) in A549 lung cancer cells. The current study is designed to investigate the detailed necroptotic signaling and its cytotoxicity on drug-resistant cancer cells. Furthermore, in vivo anticancer effects were also evaluated in nude mice model. Results: MAM directly targets receptor-interacting protein 1 (RIP1) kinase in A549 and H1299 cells, which is responsible for reactive oxygen species (ROS, mainly hydrogen peroxide) generation. A positive feedback loop between calcium (Ca2+) and c-Jun N-terminal kinase (JNK) occurred following ROS generation, leading to lysosomal membrane permeabilization and mitochondrial dysfunction. MAM showed similar cytotoxic potency toward cisplatin-resistant A549 (A549/Cis) cells by inducing necroptosis as confirmed by the protective effect of 7-Cl-O-Nec-1 (Nec-1s) and by the morphological characteristics obtained via transmission electron microscopy. Interestingly, tumor necrosis factor alpha (TNFα) was not involved in this process. Intraperitoneal injection of MAM significantly suppressed tumor growth in A549 tumor xenograft without significant body weight loss and multiorgan toxicities. Innovation and Conclusion: Our findings demonstrate that MAM induces necroptosis in A549 and H1299 lung cancer cells by targeting RIP1 kinase and ROS in a TNFα-independent manner. MAM kills A549/Cis cells with similar potency through induction of necroptosis. MAM shows anticancer effect in animal model. The present study raises the therapeutic possibility and strategy to combat cancer by the induction of necroptosis.

Neferine, a Bisbenzylisoquinoline Alkaloid, Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis.

Both the incidence and prevalence of ulcerative colitis (UC) are increasing throughout the world. Neferine, a natural alkaloid, demonstrated a variety of biological activities. In this study, the anti-inflammatory effect of neferine was investigated. Raw264.7 cells were stimulated with lipopolysaccharide (LPS) or LPS plus Z-VAD-fmk (Z-VAD). The inhibitory effect of neferine on secretion of nitrite, cytokines tumor necrosis factor alpha (TNF-[Formula: see text]) and interleukin 6 (IL-6), expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was determined. The protective effect of neferine was investigated in dextran sulfate sodium (DSS)-induced UC mouse model. Neferine significantly inhibited LPS and LPS plus Z-VAD induced secretion of nitrite, cytokines, and expression of iNOS and COX-2. Oral administration of neferine (10[Formula: see text]mg/kg and 25[Formula: see text]mg/kg) significantly reduced DSS-induced mouse weight loss, decreased disease activity index (DAI) scores, improved colon pathological changes, and decreased plasma cytokines. In addition, neferine significantly inhibited the protein expression of iNOS, COX-2, receptor-interacting protein 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL), and increased the protein expression of caspase-8 in colon tissues. These data suggest that neferine was a potent anti-inflammatory agent against LPS and DSS induced inflammation both in vitro and in vivo.

Dihydronortanshinone, a natural product, alleviates LPS-induced inflammatory response through NF-κB, mitochondrial ROS, and MAPK pathways.

Inflammation is considered to be the common pathophysiological basis for a series of diseases. Documented data showed the anti-inflammatory effects of Salvia miltiorrhiza Bunge (Danshen), a traditional herb. The pharmacological activities of dihydronortanshinone (DNT), a tanshinone isolated from Danshen, remain unknown. In this study, the anti-inflammatory effects and underlying mechanisms of DNT were investigated with a lipopolysaccharide (LPS)-induced RAW264.7 macrophage model. DNT significantly suppressed LPS-induced inflammatory mediators such as nitrite oxide (NO), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS). LPS-induced reactive oxygen species (ROS) generation was inhibited by DNT, rotenone (Rot), thenoyltrifluoroacetone (TTFA), and antimycin A (AA). Furthermore, DNT inhibited LPS-induced NF-κBp65 phosphorylation, nuclear translocation, as well as JNK1/2 and p38MAPK phosphorylation. In addition, DNT interrupted Toll-like receptor 4 (TLR4) dimerization and molecular docking results suggested that it was buried in the pocket of TLR4-MD2 complex. In conclusion, DNT inhibited LPS-induced inflammation mainly through NF-κB, mitochondrial ROS, and MAPK pathways possibly mediated by interfering LPS-TLR4-MD2 complex.

Dihydrotanshinone I, a natural product, ameliorates DSS-induced experimental ulcerative colitis in mice.

Ulcerative colitis (UC) is a chronic and relapsing inflammatory disorder of the colon and rectum with increasing morbidity in recent years. 15,16-dihydrotanshinone Ӏ (DHT) is a natural product with multiple bioactivities. In this study, we aimed to investigate the protective effect and potential mechanisms of DHT on UC. Dextran sulfate sodium salt (DSS) was administrated in drinking water for 7 days to induce UC in mice. DHT (10 and 25 mg/kg) significantly alleviated DSS-induced body weight loss, disease activity index (DAI) scores, and improved histological alterations of colon tissues. DHT inhibited the myeloperoxidase (MPO) activity, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in colon tissues and decreased serum levels of TNF-α, IL-1ß, IL-6, and high-mobility group box 1 (HMGB1). Furthermore, increased expression of kinases receptor-interacting protein 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL) and decreased expression of caspase-8 in colon tissues were partially restored by DHT. In LPS-stimulated RAW264.7 macrophages, DHT significantly inhibited generation of nitric oxide, IL-6, TNF-α and protein expression of iNOS, COX-2. In addition, increased expression of iNOS, COX-2, and phosphorylated RIP1, RIP3, MLKL in response to LPS plus Z-VAD (LZ) were also suppressed by DHT. DHT had no effect on TNF-α + BV6 + Z-VAD (TBZ) induced phosphorylation of RIPs and MLKL in HT29 cells. Especially, DHT showed no effect on LZ and TBZ-induced necroptosis in RAW264.7 and HT29 cells, respectively. In summary, DHT alleviated DSS-induced UC in mice by suppressing pro-inflammatory mediators and regulating RIPs-MLKL-caspase-8 axis.

Recent progress in doxorubicin-induced cardiotoxicity and protective potential of natural products.

BACKGROUND: As an anthracycline antibiotic, doxorubicin (DOX) is one of the most potent and widely used chemotherapeutic agents for various types of solid tumors. Unfortunately, clinical application of this drug results in severe side effects of cardiotoxicity. PURPOSE: We aim to review the research focused on elimination or reduction of DOX cardiotoxicity without affecting its anticancer efficacy by natural products. METHODS: This study is based on pertinent papers that were retrieved by a selective search using relevant keywords in PubMed and ScienceDirect. The literature mainly focusing on natural products and herb extracts with therapeutic efficacies against experimental models both in vitro and in vivo was identified. RESULTS: Current evidence revealed that multiple molecules and signaling pathways, such as oxidative stress, iron metabolism, and inflammation, are associated with DOX-induced cardiotoxicity. Based on these knowledge, various strategies were proposed, and thousands of compounds were screened. A number of natural products and herb extracts demonstrated potency in limiting DOX cardiotoxicity toward cultured cells and experimental animal models. CONCLUSIONS: Though a panel of natural products and herb extracts demonstrate protective effects on DOX-induced cardiotoxicity in cells and animal models, their therapeutic potentials for clinical needs further investigation.

Nepetoidin B, a Natural Product, Inhibits LPS-stimulated Nitric Oxide Production via Modulation of iNOS Mediated by NF-κB/MKP-5 Pathways.

Previous reports showed that nepetoidin B (NTB), a natural product isolated from many herbs, has anti-fungal and anti-bacterial effects. In this study, the antiinflammatory effect of NTB was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The cytotoxic effect of NTB and LPS was determined by MTT assay. The nitric oxide (NO) production was detected by Griess assay. The TNF-α and IL-6 levels were determined by enzyme-linked immunosorbent assay kits. Protein expressions were tested by western blotting. The transcription activity of inducible nitric oxide synthase (iNOS) was detected by luciferase assay. Immunofluorescence assay was used to observe the visualization of NF-κB/p65 nuclear translocation. NTB and LPS showed no obvious cytotoxic effect on RAW 264.7 cells. NTB remarkably inhibited LPS-induced NO and TNF-α secretion in a concentration-dependent manner while showed no significant effect on IL-6 secretion. NTB inhibited LPS-induced iNOS protein expression and transcription activity without affecting cyclooxygenase-2. Furthermore, NTB suppressed LPS-stimulated NF-κB/p65 phosphorylation and nuclear translocation. In addition, NTB significantly inhibited LPS-induced phosphorylation of JNK1/2 and p38MAPK without affecting ERK1/2. LPS-induced inhibition of mitogen-activated protein kinase phosphatase-5 (MKP-5) was completely reversed by NTB. In conclusion, these results suggested that NTB inhibited LPS-stimulated NO production possibly via modulation of iNOS mediated by MKP-5/NF-κB pathways in RAW 264.7 cells. Copyright © 2017 John Wiley & Sons, Ltd.

Cytosolic calcium mediates RIP1/RIP3 complex-dependent necroptosis through JNK activation and mitochondrial ROS production in human colon cancer cells.

Necroptosis is a form of programmed necrosis mediated by signaling complexes with receptor-interacting protein 1 (RIP1) and RIP3 kinases as the main mediators. However, the underlying execution pathways of this phenomenon have yet to be elucidated in detail. In this study, a RIP1/RIP3 complex was formed in 2-methoxy-6-acetyl-7-methyljuglone (MAM)-treated HCT116 and HT29 colon cancer cells. With this formation, mitochondrial reactive oxygen species (ROS) levels increased, mitochondrial depolarization occurred, and ATP concentrations decreased. This process was identified as necroptosis. This finding was confirmed by experiments showing that MAM-induced cell death was attenuated by the pharmacological or genetic blockage of necroptosis signaling, including RIP1 inhibitor necrostatin-1s (Nec-1s) and siRNA-mediated gene silencing of RIP1 and RIP3, but was unaffected by caspase inhibitor z-vad-fmk or necrosis inhibitor 2-(1H-Indol-3-yl)-3-pentylamino-maleimide (IM54). Transmission electron microscopy (TEM) analysis further revealed the ultrastructural features of MAM-induced necroptosis. MAM-induced RIP1/RIP3 complex triggered necroptosis through cytosolic calcium (Ca2+) accumulation and sustained c-Jun N-terminal kinase (JNK) activation. Both calcium chelator BAPTA-AM and JNK inhibitor SP600125 could attenuate necroptotic features, including mitochondrial ROS elevation, mitochondrial depolarization, and ATP depletion. 2-thenoyltrifluoroacetone (TTFA), which is a mitochondrial complex II inhibitor, was found to effectively reverse both MAM induced mitochondrial ROS generation and cell death, indicating the complex II was the ROS-producing site. The essential role of mitochondrial ROS was confirmed by the protective effect of overexpression of manganese superoxide dismutase (MnSOD). MAM-induced necroptosis was independent of TNFα, p53, MLKL, and lysosomal membrane permeabilization. In summary, our study demonstrated that RIP1/RIP3 complex-triggered cytosolic calcium accumulation is a critical mediator in MAM-induced necroptosis through sustained JNK activation and mitochondrial ROS production. Our study also provided new insights into the molecular regulation of necroptosis in human colon cancer cells.

Tanshinones and diethyl blechnics with anti-inflammatory and anti-cancer activities from Salvia miltiorrhiza Bunge (Danshen).

Four novel compounds (1-4) as well as fourteen reported compounds (5-18) were isolated and purified from Salvia miltiorrhiza Bunge (Danshen). The structures of novel compounds were determined by 1D and 2D NMR, HRESIMS data, etc. The anti-inflammatory properties of all the compounds on RAW264.7 macrophages and their cytotoxicity on H1299 and Bel-7402 cell lines coupled with a structure-activity relationship (SAR) were investigated. Compound 4 demonstrated the best anti-inflammatory activity and was chosen for further research. Compound 4 greatly suppressed secretion of nitric oxide (NO), tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) in the RAW264.7 macrophages stimulated by LPS. Additionally, the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was decreased and the nuclear translocation of NF-κB was attenuated after treatment with compound 4 in vitro. Compound 4 was able to dramatically inhibit LPS-induced activation of JNK1/2 and ERK1/2 and remarkably disrupted the TLR4 dimerization in LPS-induced RAW264.7 macrophages. Thus, the new compound 4 suppressed LPS-induced inflammation partially is due to the blocking TLR4 dimerization. In addition, the anti-cancer activity investigation indicated that most of isolated compounds exhibited cytotoxicity and the SAR analysis showed that the intact D ring was indispensable and unsaturated D ring played vital role.