bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of combination of lenvatinib and pembrolizumab in first line therapy of metastatic renal cell carcinoma
Authors: Kopyltsov E. I. , Vodolazskiy V. A. , Skoraya M. V. , Kozlov V. V.
Published: November 2022

Due to the promising results of recent trials in the treatment of metastatic renal cell cancer (mRCC) multi-drug regimens combining immunotherapy and targeted therapy in the first line are increasingly recognized. The combinations are already included in international clinical guidelines as preferred treatment options for patients with mRCC. In particular, combination of lenvatinib and pembrolizumab demonstrated high efficacy in terms of achieving a complete response, progression-free survival with a manageable toxicity profile. All adverse events on this therapy are predictable and quite well controlled. We report on our own experience of using lenvatinib plus pembrolizumab combination therapy on the example of two clinical cases of patients with intermediate prognosis mRCC.
In Vitro Mechanism of Hepatocellular Carcinoma (HepG-2) Inhibition by Activated Carbon Produced from Musca acuminata Fruit Peel
Authors: T Vimala
Published: November 2022

Cancer (CA) is global second cause of death and while drug discovery has advanced, new plant-derived medicines also need to be developed. Plant based medicinal products have many benefits as compared to the use of conventional chemical medications in minimizing the symptoms and side effects. The purpose of this study was to detect potential cytotoxicity (CYT) of activated carbon (AC) from Musca acuminata fruit peel. Significantly, the AC caused substantial increases in the synthesis of ROS, along with an attenuation of the mitochondrial (MTD) membrane potential and trigger caspase-3 activity activation in the HepG-2 cells. These findings showed that AC is a potential natural product source and provides prospects for developing new CA medicines
Acceptance and Attitudes of North Indian Population Towards COVID-19 Vaccines
Authors: Kamaljit Kaur , Varruchi Sharma , Amit Joshi , Salil Kumar , Aanchal Sharma , Seema Ramniwas , Anil K. Sharma
Published: November 2022

Coronavirus disease 2019 (COVID-19) is a pandemic which had a severe impact on all aspects of life all over the world. Vaccines are the most significant and effective interventions which are capable enough to reduce the high burden of diseases around the globe. An effective vaccine is the most anticipated resolution. The hesitancy in general public towards vaccination is a major problem for Government and health authorities as well. In this study, evaluation of health issues faced after vaccination, preferred vaccines, role of health authorities in preventing the COVID 19 disease spread, and kind of hesitancy for vaccination are discussed. Primary random data is collected from 370 individuals from north India about the COVID vaccine. The descriptive and infernal statistical tools are implemented to analyze the data using SPSS software. According to responses from the respondents’ vaccine from other countries are more effective as compared to the Indian one. Covishield vaccine was the choice of maximum respondents as compared to others. The preferencesfor the vaccination and side effects did not have any relationship whether a particular respondent got the vaccine or not. Youngers are less likely to accept COVID vaccine.
Impact of Biomedical Waste on Environment and Human health
Authors: Leena N. Meshram , Kirti J. Mhatre
Published: November 2022

Biomedical waste (BMW), if not managed properly, will pose significant environmental and health impact. Healthcare establishments have particular responsibilities with respect to the wastes they generate however, the impact of biomedical waste has not been given significant attention. Negligence in biomedical waste management contributes to environmental pollution, sickness of humans/animals, and depletes natural as well as financial resources. Poor handling of BMW pose health hazard to the hospital staff, rag-pickers, municipal workers and the community. This review focuses on impact of BMW on the environmental parameters such as water, air, soil and on human health.
In Vitro Anthelmintic Activity of Cassia fistula Against Pathogenic Liver Fluke Fasciola gigantica
Authors: H. Sen , G Swarnakar , R.N Damor , B Jogpal , H.S Chouhan
Published: November 2022

In vitro, the anthelmintic activity of Cassia fistula was studied on the pathogenic liver fluke Fasciola gigantica. Live liver flukes were collected from the infected part of the liver and bile duct of the freshly slaughtered domestic goat at the local meat market of Udaipur, India. The in vitro anthelmintic efficacy of aqueous and alcoholic extracts of Cassia fistula leaves at different concentrations of 10, 20, 30, 40, and 50 mg/ml for 2 to 10 h of exposure time were evaluated against the pathogenic liver fluke F. gigantica. The study revealed that alcoholic and aqueous extracts of C. fistula caused more mortality compared to albendazole. The alcoholic extract was more potent than the aqueous extract of C. fistula. The present research work is of significance because it would help to prepare less costly, eco-friendly, anthelmintic, and veterinary herbal drugs to replace the synthetic drugs that are currently in use.
Free Radical Scavenging Activity of Methanolic and Ethyl Acetate Extracts of Brassica oleracea and its Antioxidant Role in Combating Degenerative Diseases
Authors: K Raja , R. Saravanan
Published: November 2022

Focus on natural antioxidants in medicinal plants are gaining momentum in present days reflecting the immense valuability of Ayurveda, Naturopathy and Siddha medicine in treatment of ailments. The role played by free radicals which are highly reactive oxygen species has become increasingly relevant in etiology of degenerative diseases. The present study will focus on the antioxidant potential of methanolic and ethyl acetate extract of Brassica oleracea (var. italica) inflorescence which contribute to the scavenging of free radicals. In vitro free radical scavenging potential of aqueous extracts of Brassica oleracea inflorescence was assessed by 2,2 azino-bis (3- ethylbenzthiazoline -6-sulfonic acid, ABTS), 1,1-diphenyl-2-picryl hydrazyl (DPPH) and metal ion chelating assay (20, 40, 60, 80 and 100 μg/ml). Antioxidant potential was found more in the methanolic extracts of the florets in the present study.
Clinical significance of the series of CYP2C9*non3 variants, an unignorable predictor of warfarin sensitivity in Chinese population
Authors: Wang Dongxu , Wu Hualan , Dong Min , Zhang Qing , Zhao Anxu , Zhao Xinlong , Chong Jia , Du Minghui , Wang Yan , Shi Haifeng , Wang Shuanghu , Wang Fang , Cai Jianping , Yang Jiefu , Dai Dapeng , Chen Hao
Published: November 2022

Backgrounds

Gene polymorphisms are critical for variations in warfarin dose. To date, more than 70 CYP2C9 alleles have been identified. This study was designed to clarify the clinical significance of CYP2C9*non-3 variants to warfarin sensitivity in Chinese Han patients.

Methods

The entire CYP2C9 gene region was sequenced in 1,993 individuals, and clinical data and VKORC1 genotypes were collected from 986 patients with atrial fibrillation treated with warfarin. The SKAT-O method was used to analyze the effects of CYP2C9*non-3 variants on warfarin sensitivity.

Results

A total of 20 CYP2C9 variants were identified, of which four were novel. Carriers with CYP2C9*non-3 variants may have lower warfarin dose requirements, and similar to CYP2C9*3, CYP2C9*non-3 variants are clearly relevant to warfarin-sensitive and highly sensitive responders.

Conclusion

Our results showed that, besides CYP2C9*3, the series of CYP2C9*non-3 variants is an unignorable predictor for warfarin sensitivity in Chinese population. From a safety consideration, people carried such variants may need a preferred choice of NOACs when they started anticoagulation therapy.
An unusual contrast-induced encephalopathy following percutaneous coronary intervention in patients with cerebrovascular abnormalities: A case report
Authors: Liao Jiangquan , Wang Yan , Shao Mingjing , Wang Yanling , Du Jinhang , Li Xianlun , Yang Peng , Fu Dongliang , Dong Zhe , Liu Mengru
Published: November 2022

Introduction

Contrast-induced encephalopathy (CIE) is a complication associated with the administration of iodinated contrast, which usually happens minutes to hours after contact with contrast, and fully recovers within 72 h. The clinical manifestations of CIE are diverse, and the pathological mechanism is not explicit.

Methods

We report the case of a 66-year-old female who suffered from a delayed CIE following the administration of iodinated contrast agent. Symptoms were severe. Imaging examination, biochemical and etiological detection were performed timely. The course of neurological symptoms was atypical. Her complex complications of hypothyroidism and cerebrovascular abnormalities contributed to more challenges, which were also clues to the diagnosis. With prompt and active treatment, the patient recovered fully over 10 days.

Discussion

The diagnosis standard of CIE highly depends on the association with the contact of contrast and the exclusion of other nervous system diseases. Complicated clinical circumstances and individual specificity can lead to different clinical manifestations of CIE, making it even more difficult to diagnose and treat. Prompt and dynamic imaging examination would provide great value in the diagnosis and evaluation of CIE. Timely diagnosis and intervention may be the key to its satisfying prognosis.
Which one? A suggested approach for evaluating digital health maturity models
Authors: Woods Leanna , Eden Rebekah , Duncan Rhona , Kodiyattu Zack , Macklin Sophie , Sullivan Clair
Published: November 2022

Background

Digital health maturity models allow healthcare organizations to evaluate digital health capability and to develop roadmaps for improving patient care through technology. There are many models available commercially for healthcare providers to use to assess their digital health maturity. Currently, there are limited evidence-based methods to assess the quality, utility, and efficacy of maturity models to select the most appropriate model for the given context.

Objective

To develop a framework to assess digital maturity models and facilitate recommendations for digital maturity model selection.

Methods

A systematic, consultative, and iterative process was used. Literature analyses and a stakeholder needs analysis (n = 23) was conducted to develop content and design considerations. These considerations were incorporated into the initial version of the framework developed by researchers in a design workshop. External stakeholder review (n = 20) and improvements strengthened and finalized the framework.

Results

The criteria of the framework include assessment of healthcare context, feasibility, integrity, completeness and actionability. Users can compare model performance in order to select the most appropriate model for their context.

Conclusion

The framework provides healthcare stakeholders with a consistent and objective methodology to compare digital health maturity models, informing approaches to choosing a suitable model. This is a critical step as healthcare evolves towards a digital health system focused on improving the quality of care, reducing costs and improving the provider and consumer experience.
Blood glucose may be another index to initiate insulin treatment besides glycated hemoglobin A1c after oral antidiabetic medications failure for glycemic control: A real–world survey
Authors: Li Yanli , Wu Yan , Shu Yi , Li Shu , Pei Jianhao , Chen Hong , Liu Shiping , Xiang Guangda , Wang Wenbo , Shan Pengfei , Su Heng , Wu Xiaoyan , Yan Dewen , Li Wangen
Published: November 2022

Objective

The inertia of insulin initiation is a barrier to achieving glycemic control when oral antidiabetic drugs fail to control glucose during the treatment of type 2 diabetes (T2D). Insulin initiation is usually based on glycated hemoglobin A1c (A1C). To investigate whether there is another index for insulin initiation besides A1C, we conducted a cross-sectional survey in the real world.

Methods

We conducted a multicenter cross-section survey with a total of 1034 T2D patients. All patients, at the time of the survey, decided to initiate insulin therapy due to failure of controlling glucose using only oral antidiabetic drugs. We analyzed the differences of blood glucose between patients who were tested for A1C and those who were not.

Results

666 (64.4%) patients were tested A1C and 368 (35.6%) were not. Neither fasting blood glucose (FBG) (12.0 ± 2.9 vs 12.3 ± 2.9 mmol/L, t = 1.494, P = 0.135) nor postprandial blood glucose (PBG) (18.4 ± 4.8 vs 17.9 ± 4.8 mmol/L, t = 1.315, P = 0.189) were significantly different between patients with and without A1C.

Conclusion

Our results demonstrated that initiating insulin based on FBG or PBG is a common clinical practice, at least in China; moreover, since it is easier to obtain than A1C, it can be a simple and effective way to overcome clinical inertia for initiating insulin.
Should electric vehicle subsidies phase down? An insight from the analysis of the increasingly competitive automobile market
Authors: Wu Fulan , Li Pei , Lu Yuanzhu , Dong Xuebing
Published: November 2022

Electric vehicles are expanding significantly in recent years. Policies have been critical in stimulating the growth of electric vehicle market. This paper focuses on subsidy policies for electric vehicle adoption in a horizontally differentiated goods market. Using a representative consumer model and assuming the duopoly firms compete in a Cournot fashion, we find that the optimal level of subsidies might not fall as a result of the decreasing production cost of electric vehicles. Instead, the subsidy might phase down when the government starts to bring more competition into the electric vehicle industry. This main result goes through irrespective of whether the subsidy is sales volume-based or sales revenue-based. Our numerical findings further suggest that welfare maximizing subsidy declines with an increasing competition among car manufacturers, and sales volume-based subsidy policy is more efficient than sales revenue-based one. In addition, we also find that the subsidy cut would reduce electric vehicle sales, and subsidy policy is responsive to the government’s objective function.
Evolution and attribution of the water yield coefficient in the Yiluo river basin
Authors: Hou Jun , Yan Denghua , Qin Tianling , Liu Shanshan , Yan Sheng , Li Jian , Abebe Sintayehu A. , Cao Xuchao
Published: November 2022

Our aim in this research was to detect historical and future water yield coefficient evolution and attribution. Based on the calibrated and validated water yield coefficient model in the Yiluo River Basin, the coefficient for the years 2000–2020 was simulated, along with the future projection for 2030–2050 under four Shared Socioeconomic Pathways (SSP126, SSP245, SSP370, and SSP585). The spatio-temporal evolution of historical and future water yield coefficients was then analyzed. Moreover, the geographical detector model was used to detect the impacts of climate, land use, and terrain factors on the water yield coefficient. The results showed that the water yield coefficient increased by 8.53% from 2000 to 2020, with the coefficient of farmland increasing by 10.47% and that of forestland decreasing by 8.93%. The coefficient was highest under the SSP370 scenario and the lowest under the SSP585 scenario in projections for 2030–2050. Compared to 2000–2020, the coefficients of the two scenarios increased by 12.2% and 2.0%, respectively. Consequently, under the SSP370 and SSP585 scenarios, the coefficient of farmland increased by 13.2% and 2.7%, and that of the forestland decreased by 0.9% and 14.6%, respectively. Driving factors detection indicated that land use types had the strongest explanatory power affecting the water yield coefficient; the explanatory value reached 26.5% in 2000–2020 and will exceed 29.5% in 2030–2050. In addition, the interaction between any two factors was stronger than a single factor. This research provides scientific support for the precise management of watershed and water-land resources.
Food preferences in a generalist pollen feeder: A nutritional strategy mainly driven by plant carbohydrates
Authors: Bellec Laura , Cortesero Anne-Marie , Giguère Thomas , Faure Sébastien , Hervé Maxime R.
Published: November 2022

Introduction

Animal nutritional strategies have been extensively studied in vertebrates, where generalism at the individual scale is the rule. In insect herbivores, the determinants of the nutritional strategy of individual-scale generalists remain poorly studied, and the focus has been placed mainly on the influence of plant defense. Moreover, the integration of a physiological dimension in such studies remains rare. Here, we investigated the determinants of the nutritional strategy of pre-diapausing pollen beetles,Brassicogethes aeneus, with a focus on the influence of macronutrients. Before their diapause, pollen beetles are known to feed from plants belonging to many different families. This raises three questions: (i) Is the generalism of pollen beetles a populational consequence of individuals specialized on different plant families? (ii) Do individuals feed at random on flowers available or do they have a particular nutritional strategy? and (iii) In case of non-random feeding choices, do pollen macronutrients explain this nutritional strategy?

Methods

To answer these questions, we used a series of laboratory experiments including feeding choice tests on flowers and artificial substrates, quantification of pollen nutrient content, quantification of the insect energetic budget, and performance experiments.

Results

We show that pollen beetles are generalist at the individual scale, and that clear and stable food preferences are established over a few hours in a multi-choice context. Pollen beetles prefer to feed on flowers with a carbohydrate-rich pollen, and this preference is adaptive since performance correlates positively with the plant carbohydrate content. This better performance may be explained by the fact that individuals feeding on carbohydrate-rich resources accumulate more glycogen and total energetic reserves.

Discussion

This study represents one of the few evidences of generalism at the individual scale in an herbivorous insect. It provides a better understanding of the nutritional strategy of a non-bee pollen feeder and shows the importance of carbohydrates in this strategy. It highlights the need to combine assessments of the plant macronutrient content and insect energetic budget in an adaptive framework to better understand the nutritional strategies of herbivores.
The dual role of the CD95 and CD95L signaling pathway in glioblastoma
Authors: Zhang Yanrui , Jin Taian , Dou Zhangqi , Wei Boxing , Zhang Buyi , Sun Chongran
Published: November 2022

Binding of CD95, a cell surface death receptor, to its homologous ligand CD95L, transduces a cascade of downstream signals leading to apoptosis crucial for immune homeostasis and immune surveillance. Although CD95 and CD95L binding classically induces programmed cell death, most tumor cells show resistance to CD95L-induced apoptosis. In some cancers, such as glioblastoma, CD95-CD95L binding can exhibit paradoxical functions that promote tumor growth by inducing inflammation, regulating immune cell homeostasis, and/or promoting cell survival, proliferation, migration, and maintenance of the stemness of cancer cells. In this review, potential mechanisms such as the expression of apoptotic inhibitor proteins, decreased activity of downstream elements, production of nonapoptotic soluble CD95L, and non-apoptotic signals that replace apoptotic signals in cancer cells are summarized. CD95L is also expressed by other types of cells, such as endothelial cells, polymorphonuclear myeloid-derived suppressor cells, cancer-associated fibroblasts, and tumor-associated microglia, and macrophages, which are educated by the tumor microenvironment and can induce apoptosis of tumor-infiltrating lymphocytes, which recognize and kill cancer cells. The dual role of the CD95-CD95L system makes targeted therapy strategies against CD95 or CD95L in glioblastoma difficult and controversial. In this review, we also discuss the current status and perspective of clinical trials on glioblastoma based on the CD95-CD95L signaling pathway.
Manipulation of diacylglycerol and ERK-mediated signaling differentially controls CD8+ T cell responses during chronic viral infection
Authors: Harabuchi Shohei , Khan Omar , Bassiri Hamid , Yoshida Taku , Okada Yohei , Takizawa Masaomi , Ikeda Osamu , Katada Akihiro , Kambayashi Taku
Published: November 2022

Introduction

Activation of T cell receptor (TCR) signaling is critical for clonal expansion of CD8+ T cells. However, the effects of augmenting TCR signaling during chronic antigen exposure is less understood. Here, we investigated the role of diacylglycerol (DAG)-mediated signaling downstream of the TCR during chronic lymphocytic choriomeningitis virus clone 13 (LCMV CL13) infection by blocking DAG kinase zeta (DGKζ), a negative regulator of DAG.

Methods

We examined the activation, survival, expansion, and phenotype of virus-specific T cell in the acute and chronic phases of LCMV CL13-infected in mice after DGKζ blockade or selective activation of ERK.

Results

Upon LCMV CL13 infection, DGKζ deficiency promoted early short-lived effector cell (SLEC) differentiation of LCMV-specific CD8+ T cells, but this was followed by abrupt cell death. Short-term inhibition of DGKζ with ASP1570, a DGKζ-selective pharmacological inhibitor, augmented CD8+ T cell activation without causing cell death, which reduced virus titers both in the acute and chronic phases of LCMV CL13 infection. Unexpectedly, the selective enhancement of ERK, one key signaling pathway downstream of DAG, lowered viral titers and promoted expansion, survival, and a memory phenotype of LCMV-specific CD8+ T cells in the acute phase with fewer exhausted T cells in the chronic phase. The difference seen between DGKζ deficiency and selective ERK enhancement could be potentially explained by the activation of the AKT/mTOR pathway by DGKζ deficiency, since the mTOR inhibitor rapamycin rescued the abrupt cell death seen in virus-specific DGKζ KO CD8+ T cells.

Discussion

Thus, while ERK is downstream of DAG signaling, the two pathways lead to distinct outcomes in the context of chronic CD8+ T cell activation, whereby DAG promotes SLEC differentiation and ERK promotes a memory phenotype.
Plasma adsorption in refractory chronic gouty arthritis flare: A case report
Authors: Lei Yan , Cui Tian-Jiao , Wang Xiao-Hua , Zhang Xue-Mei , Tang Chun , Zheng Zhi-Hua
Published: November 2022

Background

Along with uric acid, which is the primary driving factor of gout, downstream inflammatory mediators have been shown to be involved in the pathogenesis of gouty arthritis flares. Extracorporeal haemadsorption is an emerging technology for the treatment of dysregulated inflammatory states by effectively removing cytokines from the bloodstream. Whether haemadsorption was effective in refractory gout flares has not been reported in the literature.

Case summary

We report the case of a 52-year-old male who presented with refractory gouty arthropathy for 30 years. His uric acid levels were poorly controlled due to poor diet and treatment compliance. Tophi were found to have precipitated in multiple joints and subcutaneous tissue. In the last 2 years, his incidents of gouty flares had become more frequent, and resistant to the medications, including colchicine, allopurinol, febuxostat, glucocorticoids, and NSAID analgesics. He had experienced a triad of chills, high fever and arthritis for the past 2 weeks. Therefore, he took 2 mg colchicine twice daily for 2 weeks with no improvement in his pain. Proinflammatory cytokines, such as interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α), were found to be remarkably elevated. Given that conventional treatment was unsuccessful, we tried to employ plasma adsorption (PA) to remove inflammatory cytokines. After 4 sessions, symptoms, such as fever, joint swelling and pain, were greatly improved. Meanwhile, the levels of proinflammatory factors such as IL-6 and TNF-α were found to be decreased, while the anti-inflammatory factor IL-10 remained the same during the course. He was followed up for 8 months and arthritis have flared up twice in response to a high-purine diet.

Conclusion

Our study suggests that plasma adsorption (PA) may be a promising and feasible treatment for refractory gout when conventional treatments are unsatisfactory or contraindicated. However, more clinical trials are needed to verify the efficacy and safety of the treatment.

Core tip

Chronic gouty arthritis flares are refractory to conventional treatment, such as uric acid-lowering drugs and NSAID analgesics. Due to the involvement of inflammatory cytokines, plasma adsorption was employed to alleviate flares by removing inflammatory mediators. Herein, we report a 52-year-old male who presented with refractory gouty arthropathy for 30 years, manifested with a triad of chills, high fever and arthritis. He underwent several sessions of plasma adsorption, and his symptoms soon improved, along with a drop in inflammatory mediators. We conclude that plasma adsorption may be a promising and feasible treatment for refractory gout when conventional treatments are unsatisfactory or contraindicated.
Identification and experimental validation of a tumor-infiltrating lymphocytes–related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma
Authors: Deng Yulin , Guo Kai , Tang Zhenfeng , Feng Yuanfa , Cai Shanghua , Ye Jianheng , Xi Yuanxue , Li Jinchuang , Liu Ren , Cai Chao , Tan Zeheng , Zhang Yixun , Han Zhaodong , Zeng Guohua , Zhong Weide
Published: November 2022

Clear cell renal cell carcinoma (ccRCC) is a common aggressive malignant tumor of the urinary system. Given the heterogeneity of the tumor microenvironment, immunotherapy may not fully exert its role in the treatment of advanced patients. Long noncoding RNA (lncRNA) has been reported to be critically associated with the differentiation and maturation of tumor-infiltrating lymphocytes (TILs), which work against tumor cells. In this study, we identified 10 TIL-related lncRNAs (AL590094.1, LINC02027, LINC00460, AC147651.1, AC026401.3, LINC00944, LINC01615, AP000439.2, AL162586.1, and AC084876.1) by Pearson correlation, univariate Cox regression, Lasso regression, and multivariate Cox regression based on The Cancer Genome Atlas (TCGA) database. A risk score model was established based on these lncRNAs. Next, a nomogram was constructed to predict the overall survival. By employing differentially expressed genes (DEGs) between groups with high and low risk scores, gene ontology (GO) enrichment analysis was performed to identify the major biological processes (BP) related to immune DEGs. We analyzed the mutation data of the groups and demonstrated that SETD2 and BAP1 had the highest mutation frequency in the high-risk group. The “CIBERSORT” R package was used to detect the abundance of TILs in the groups. The expression of lymphocyte markers was compared. We also determined the expression of two lncRNAs (AC084876.1 and AC026401.3) and their relationship with lymphocyte markers in the kidney tissue of ccRCC patients and showed that there was a positive correlation between AC084876.1 and FoxP3. Proliferation, migration, and invasion of AC084876.1-downregulated ccRCC cell lines were inhibited, and the expression of PD-L1 and TGF-β secretion decreased. To our knowledge, this is the first bioinformatics study to establish a prognostic model for ccRCC using TIL-related lncRNAs. These lncRNAs were associated with T-cell activities and may serve as biomarkers of disease prognosis.
A pregnancy hormone-cell death link promotes enhanced lupus-specific immunological effects
Authors: Sachdeva Ruchi , Pal Rahul
Published: November 2022

Women of reproductive age demonstrate an increased incidence of systemic lupus erythematosus, and reproductive hormones have been implicated in disease progression. Additionally, pregnancy can be associated with disease “flares”, the reasons for which remain obscure. While apoptotic bodies are believed to provide an autoantigenic trigger in lupus, whether autoantigenic constituents vary with varying cellular insults, and whether such variations can be immunologically consequential in the context of pregnancy, remains unknown. As assessed by antigenicity and mass spectrometry, apoptotic bodies elicited by different drugs demonstrated the differential presence of lupus-associated autoantigens, and varied in the ability to elicit lupus-associated cytokines from lupus splenocytes and alter the phenotype of lupus B cells. Immunization of tamoxifen-induced apoptotic bodies in lupus-prone mice generated higher humoral autoreactive responses than did immunization with cisplatin-induced apoptotic bodies, and both apoptotic bodies were poorly immunogenic in healthy mice. Incubation of lupus splenocytes (but not healthy splenocytes) with the pregnancy hormone human chorionic gonadotropin (hCG) along with tamoxifen-induced apoptotic bodies (but not cisplatin-induced apoptotic bodies) induced increases in the secretion of lupus-associated cytokines and in the up-modulation of B cell phenotypic markers. In addition, levels of secreted autoantibodies (including of specificities linked to lupus pathogenesis) were enhanced. These events were associated with the heightened phosphorylation of several signaling intermediates. Observations suggest that hCG is a potential disease-promoting co-stimulant in a lupus-milieu; when combined with specific apoptotic bodies, it enhances the intensity of multiple lupus-associated events. These findings deepen mechanistic insight into the hormone’s links with autoreactive responses in lupus-prone mice and humans.
Case report: Evolution of pulmonary manifestations and virological markers in critical COVID-19 infection in Bruton’s agammaglobulinemia
Authors: Rise Nina , Touborg Toke , Lundsted Ditte Helene , Dalager-Pedersen Michael , Mogensen Trine H.
Published: November 2022

Despite several reports and small case series on the disease course of SARS-CoV-2 infection in patients with inborn errors of immunity (IEI), including X-linked agammaglobulinemia (XLA), this topic remains incompletely described. Here we present the case of a 38-year-old unvaccinated man with XLA, who acquired SARS-CoV-2 infection and experienced a protracted disease course with 47 days of SARS-CoV-2 positivity, critical COVID-19 with respiratory insufficiency necessitating intensive care and ventilatory support, and prompting repeated intensified treatments with remdesivir, dexamethasone, and monoclonal antibodies to eventually control infection. We describe the disease course and treatment and review the current literature on COVID-19 susceptibility and evidence for vaccine efficacy in patients with XLA.
LATPS, a novel prognostic signature based on tumor microenvironment of lung adenocarcinoma to better predict survival and immunotherapy response
Authors: Huang Jihong , Yuan Lu , Huang Wenqi , Liao Liwei , Zhu Xiaodi , Wang Xiaoqing , Li Jiaxin , Liang Wenyu , Wu Yuting , Liu Xiaocheng , Yu Dong , Zheng Yunna , Guan Jian , Zhan Yongzhong , Liu Laiyu
Published: November 2022

Background

Clinically, only a minority of patients benefit from immunotherapy and few efficient biomarkers have been identified to distinguish patients who would respond to immunotherapy. The tumor microenvironment (TME) is reported to contribute to immunotherapy response, but details remain unknown. We aimed to construct a prognostic model based on the TME of lung adenocarcinoma (LUAD) to predict the prognosis and immunotherapy efficacy.

Methods

We integrated computational algorithms to describe the immune infiltrative landscape of LUAD patients. With the least absolute shrinkage and selection operator (LASSO) and Cox regression analyses, we developed a LUAD tumor microenvironment prognostic signature (LATPS). Subsequently, the immune characteristics and the benefit of immunotherapy in LATPS-defined subgroups were analyzed. RNA sequencing of tumor samples from 28 lung cancer patients treated with anti-PD-1 therapy was conducted to verify the predictive value of the LATPS.

Results

We constructed the LATPS grounded on four genes, including UBE2T, KRT6A, IRX2, and CD3D. The LATPS-low subgroup had a better overall survival (OS) and tended to have a hot immune phenotype, which was characterized by an elevated abundance of immune cell infiltration and increased activity of immune-related pathways. Additionally, tumor immune dysfunction and exclusion (TIDE) score was markedly decreased in the LATPS-low subgroup, indicating an enhanced opportunity to benefit from immunotherapy. Survival analysis in 28 advanced lung cancer patients treated with an anti-PD-1 regimen at Nanfang hospital revealed that the LATPS-low subgroup had better immunotherapy benefit.

Conclusion

LATPS is an effective predictor to distinguish survival, immune characteristics, and immunotherapy benefit in LUAD patients.
Candida albicans V132 induces trained immunity and enhances the responses triggered by the polybacterial vaccine MV140 for genitourinary tract infections
Authors: Martín-Cruz Leticia , Angelina Alba , Baydemir Ilayda , Bulut Özlem , Subiza José Luis , Netea Mihai G. , Domínguez-Andrés Jorge , Palomares Oscar
Published: November 2022

Introduction

Recurrent urinary tract infections (RUTIs) and recurrent vulvovaginal candidiasis (RVVCs) represent major healthcare problems all over the world. Antibiotics and antifungals are widely used for such infectious diseases, which is linked with microbial resistances and microbiota deleterious effects. The development of novel approaches for genitourinary tract infections (GUTIs) such as trained immunity-based vaccines (TIbV) is therefore highly required. MV140 is a sublingual whole-cell heat-inactivated polybacterial preparation with demonstrated clinical efficacy for RUTIs. The sublingual heat-inactivated Candida albicans vaccine V132 has been developed for RVVCs. We previously showed that the combination of MV140 and V132 promotes potent Th1/Th17 and regulatory T-cell responses against antigens contained in the formulation and unrelated antigens. The specific contribution of each preparation to such effects and the underlying molecular mechanisms remain incompletely understood.

Methods

PBMC and monocytes were isolated from healthy donors and in vitro stimulated with V132, MV140 or MV140/V132. After 6 days of resting, cells were reestimulated with LPS and MV140. Analysis of cytokine production by ELISA, Seahorse assays for functional metabolic experiments and chromatin immunoprecipitation assays were performed. BALB/c mice were intraperitoneally and sublingually immunized with V132.

Results

We uncover that V132 induces trained immunity in human PBMCs and purified monocytes, significantly increasing the responses triggered by subsequent stimulation with MV140. Mechanistically, V132 drives metabolic rewiring towards increased glycolysis and oxidative phosphorylation and induces epigenetic reprogramming that enhances the transcription of the pro-inflammatory genes IL6 and TNFA. Splenocytes and peritoneal cells from V132-immunize mice show increased responses upon in vitro stimulation with MV140. Remarkably, splenocytes from sublingually V132-immunized and MV140 in vivo treatment mice show stronger Th17 responses than mice exposed to excipients upon in vitro stimulation with MV140.

Conclusion

Overall, we provide novel mechanistic insights into how V132-induced trained immunity enhances both innate and adaptive immune responses triggered by MV140, which might open the door for new interventions for GUTIs with important clinical implications.
Feeding tea polysaccharides affects lipid metabolism, antioxidant capacity and immunity of common carp (Cyprinus carpio L.)
Authors: Yang Guokun , Liang Xiaomin , Hu Jihong , Li Chengquan , Hu Wenpan , Li Keke , Chang Xulu , Zhang Yanmin , Zhang Xindang , Shen Yawei , Meng Xiaolin
Published: November 2022

Tea polysaccharides plays a role in lipid metabolism, antioxidant capacity and immunity of mammals. To investigate the functions of tea polysaccharides on fish, the common carp (Cyprinus carpio L.) was selected as the animal model in this study. In our study, the common carp (45±0.71g) were randomly divided into four groups and were fed fodder with 50% carbohydrate. The common carp were orally administrated with 0 mg/kg BW (control group), 200 mg/kg BW (low-dose group), 400 mg/kg BW (medium-dose group) and 800 mg/kg BW (high-dose group) tea polysaccharide for two week. At the end of experiment, the serum glucose, TG, MDA contents and antioxidase activities were measured by commercial kits. The serum immune factors levels were tested by ELISA. The genes expression levels related to antioxidant capacity, metabolism and immunity were measured by real-time PCR. The results showed that the glucose, TG and MDA contents in serum were significantly decreased by tea polysaccharides treatment. The serum activities of SOD were significantly increased by low-dose tea polysaccharides treatment. The serum activities of GPX were significantly increased by medium-dose tea polysaccharides treatment. The serum levels of IL-1β and TNFα were significantly decreased in the tea polysaccharides treatment group. In the high-dose treatment group, the serum level of TGFβ was significantly increased, and the serum level of IL-12 was markedly decreased. In the hepatopancreas, the expression of acc1, fas, srebp1c, lpl, gys and pparγ were significantly reduced, and the expression of pygl, cat, mnsod, ho-1 and gr were significantly up-regulated in the tea polysaccharides group. In the intestine, the expression of zo-1, occ and gip was significantly up-regulated in the high-dose treatment group. Moreover, the expression of glut2 and sglt1 were significantly down regulated. In the spleen, the expression of il-12, tnfα and il-6 were significantly decreased, and the expression of il-10 and tgfβ was significantly increased by the tea polysaccharides. In the spleen cells, the tea polysaccharides could relieve the LPS-induced immune damage. In conclusion, tea polysaccharides can improve antioxidant capacity, lipid metabolism and immunity of common carp.
Acidic Microenvironments Found in Cutaneous Leishmania Lesions Curtail NO-Dependent Antiparasitic Macrophage Activity
Authors: Frick Linus , Hinterland Linda , Renner Kathrin , Vogl Marion , Babl Nathalie , Heckscher Simon , Weigert Anna , Weiß Susanne , Gläsner Joachim , Berger Raffaela , Oefner Peter J. , Dettmer Katja , Kreutz Marina , Schatz Valentin , Jantsch Jonathan
Published: November 2022

Local tissue acidosis affects anti-tumor immunity. In contrast, data on tissue pH levels in infected tissues and their impact on antimicrobial activity is sparse. In this study, we assessed the pH levels in cutaneousLeishmanialesions.Leishmania major-infected skin tissue displayed pH levels of 6.7 indicating that lesional pH is acidic. Next, we tested the effect of low extracellular pH on the ability of macrophages to produce leishmanicidal NO and to fight the protozoan parasiteLeishmania major. Extracellular acidification led to a marked decrease in both NO production and leishmanicidal activity of lipopolysaccharide (LPS) and interferon γ (IFN-γ)-coactivated macrophages. This was not directly caused by a disruption of NOS2 expression, a shortage of reducing equivalents (NAPDH) or substrate (L-arginine), but by a direct, pH-mediated inhibition of NOS2 enzyme activity. Normalization of intracellular pH significantly increased NO production and antiparasitic activity of macrophages even in an acidic microenvironment. Overall, these findings indicate that low local tissue pH can curtail NO production and leishmanicidal activity of macrophages.
Modulating macrophage function to reinforce host innate resistance against Mycobacterium avium complex infection
Authors: Park Hyun-Eui , Lee Wonsik , Choi Sangwon , Jung Myunghwan , Shin Min-Kyoung , Shin Sung Jae
Published: November 2022

Mycobacterium aviumcomplex (MAC) is the main causative agent of infectious diseases in humans among nontuberculous mycobacteria (NTM) that are ubiquitous organisms found in environmental media such as soil as well as in domestic and natural waters. MAC is a primary causative agent of NTM-lung disease that threaten immunocompromised or structural lung disease patients. The incidence and the prevalence ofM. tuberculosisinfection have been reduced, while MAC infections and mortality rates have increased, making it a cause of global health concern. The emergence of drug resistance and the side effects of long-term drug use have led to a poor outcome of treatment regimens against MAC infections. Therefore, the development of host-directed therapy (HDT) has recently gained interest, aiming to accelerate mycobacterial clearance and reversing lung damage by employing the immune system using a novel adjuvant strategy to improve the clinical outcome of MAC infection. Therefore, in this review, we discuss the innate immune responses that contribute to MAC infection focusing on macrophages, chief innate immune cells, and host susceptibility factors in patients. We also discuss potential HDTs that can act on the signaling pathway of macrophages, thereby contributing to antimycobacterial activity as a part of the innate immune response during MAC infection. Furthermore, this review provides new insights into MAC infection control that modulates and enhances macrophage function, promoting host antimicrobial activity in response to potential HDTs and thus presenting a deeper understanding of the interactions between macrophages and MACs during infection.
Platelet-rich plasma in alopecia areata and primary cicatricial alopecias: A systematic review
Authors: Tejapira Kasama , Yongpisarn Tanat , Sakpuwadol Nawara , Suchonwanit Poonkiat
Published: November 2022

Background

Immune-mediated alopecias (IMAs), a group of hair disorders associated with immunological reactions, remain a therapeutic challenge since available treatments are generally unfavorable with potential side effects. Platelet-rich plasma (PRP) has been recently proposed as a treatment option based on several limited-quality studies; however, there is no systematic evaluation of PRP efficacy on IMAs in the literature.

Objective

To assess PRP’s effects in treating IMAs using a systematic review.

Methods

Electronic searches were conducted using PubMed, Embase, Scopus, and Cochrane Library databases. A search strategy was designed to retrieve all studies exploring PRP in treating IMAs, including alopecia areata (AA) and primary cicatricial alopecias (PCAs). In addition, all randomized and non-randomized studies reporting subjective and/or objective outcomes of alopecia treatment with PRP were included.

Results

Thirty-two studies were included, comprising 621 patients with AA and 19 patients with PCAs. PRP had superior efficacy as monotherapy in five studies, comparable to intralesional corticosteroids in six studies in AA treatment. In addition, in the analysis of PCAs, including lymphocytic and neutrophilic subtypes, PRP was efficacious in alleviating disease progression in nine studies.

Conclusion

PRP is considered a promising treatment for AA and PCAs in patients who experienced unfavorable outcomes from conventional treatment. However, its clinical application remains to be standardized, and its recommendation as a treatment for IMAs could not be ascertained due to a lack of high-quality evidence.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=353859], identifier [CRD42022353859].
phoD-harboring bacterial community composition dominates organic P mineralization under long-term P fertilization in acid purple soil
Authors: Lang Ming , Li Haoming , Lakshmanan Prakash , Chen Yuanxue , Chen Xinping
Published: November 2022

Introduction

A better understanding of the regulatory role of microorganisms on soil phosphorous (P) mobilization is critical for developing sustainable fertilization practices and reducing P resource scarcity. The phoD genes regulate soil organic P (Po) mobilization.

Methods

Based on the long-term P application experiments in acid purple soil of maize system in Southwest China (started in 2010), the experiment included five P levels: 0, 16, 33, 49, and 65.5 kg P hm–2 (P0, P16, P33, P49, and P65.5, respectively). The molecular speciation of organic P in soil was determined by 31P-nuclear magnetic resonance (NMR), high-throughput sequencing technology, and real-time qPCR were used to analyze the bacterial community and abundance of phoD-harboring bacterial genes, exploring the bacterial community and abundance characteristics of phoD gene and its relationship with the forms of Po and alkaline phosphatase (ALP) activity in the soil.

Results

The results showed that the orthophosphate monoesters (OM) were the main Po speciation and varied by P fertilization in acid purple soil. ALP activity decreased as P fertilization increased. Co-occurrence network analysis identified the overall network under five P fertilizations. The keystone taxon base on the network showed that Collimonas, Roseateles, Mesorhizobium, and Cellulomonas positively correlated with both OM and Po. The random forest showed that Cellulomonas, Roseateles, and Rhodoplanes were the key predictors for ALP activity. The keystone taxon was a more important predictor than the dominant taxon for ALP, OM, and Po. The structural equation model (SEM) showed that soil organic matter (SOM), available P (AP), and OM were the main factors influencing the ALP by reshaping phoD-harboring bacteria alpha diversity, community composition, and phoD abundance.

Discussion

The phoD-harboring bacterial community composition especially the keystone taxon rather than alpha diversity and abundance dominated the ALP activity, which could promote P utilization over an intensive agroecosystem. These findings improve the understanding of how long-term gradient fertilization influences the community composition and function of P-solubilizing microorganisms in acid purple soil.