bluuebunny/crossref_metadata_2025 huggingface dataset:
Excessive Activation of Notch Signaling in Macrophages Promote Kidney Inflammation, Fibrosis, and Necroptosis
Authors: Ma Tiankui , Li Xin , Zhu Yonghong , Yu Shufan , Liu Tianyan , Zhang Xiaodan , Chen Dong , Du Shuyan , Chen Tong , Chen Shuo , Xu Yanyan , Fan Qiuling
Published: February 2022

Diabetic nephropathy (DN) is one of the main causes of end-stage renal disease (ESRD). Existing treatments cannot control the progression of diabetic nephropathy very well. In diabetic nephropathy, Many monocytes and macrophages infiltrate kidney tissue. However, the role of these cells in the pathogenesis of diabetic nephropathy has not been fully elucidated. In this study, we analyzed patient kidney biopsy specimens, diabetic nephropathy model animals. Meanwhile, we cocultured cells and found that in diabetic nephropathy, damaged intrinsic renal cells (glomerular mesangial cells and renal tubular epithelial cells) recruited monocytes/macrophages to the area of tissue damage to defend against and clear cell damage. This process often involved the activation of different types of macrophages. Interestingly, the infiltrating macrophages were mainly M1 (CD68+iNOS+) macrophages. In diabetic nephropathy, crosstalk between the Notch pathway and NF-κB signaling in macrophages contributed to the polarization of macrophages. Hyperpolarized macrophages secreted large amounts of inflammatory cytokines and exacerbated the inflammatory response, extracellular matrix secretion, fibrosis, and necroptosis of intrinsic kidney cells. Additionally, macrophage depletion therapy with clodronate liposomes and inhibition of the Notch pathway in macrophages alleviated the pathological changes in kidney cells. This study provides new information regarding diabetic nephropathy-related renal inflammation, the causes of macrophage polarization, and therapeutic targets for diabetic nephropathy.
A Paradoxical Effect of Interleukin-32 Isoforms on Cancer
Authors: Shim Saerok , Lee Siyoung , Hisham Yasmin , Kim Sinae , Nguyen Tam T. , Taitt Afeisha S. , Hwang Jihyeong , Jhun Hyunjhung , Park Ho-Young , Lee Youngmin , Yeom Su Cheong , Kim Sang-Yeob , Kim Yong-Gil , Kim Soohyun
Published: February 2022

IL-32 plays a contradictory role such as tumor proliferation or suppressor in cancer development depending on the cancer type. In most cancers, it was found that the high expression of IL-32 was associated with more proliferative and progression of cancer. However, studying the isoforms of IL-32 cytokine has placed its paradoxical role into a wide range of functions based on its dominant isoform and surrounding environment. IL-32β, for example, was found mostly in different types of cancer and associated with cancer expansion. This observation is legitimate since cancer exhibits some hypoxic environment and IL-32β was known to be induced under hypoxic conditions. However, IL-32θ interacts directly with protein kinase C-δ reducing NF-κB and STAT3 levels to inhibit epithelial-mesenchymal transition (EMT). This effect could explain the different functions of IL-32 isoforms in cancer. However, pro- or antitumor activity which is dependant on obesity, gender, and age as it relates to IL-32 has yet to be studied. Obesity-related IL-32 regulation indicated the role of IL-32 in cancer metabolism and inflammation. IL-32-specific direction in cancer therapy is difficult to conclude. In this review, we address that the paradoxical effect of IL-32 on cancer is attributed to the dominant isoform, cancer type, tumor microenvironment, and genetic background. IL-32 seems to have a contradictory role in cancer. However, investigating multiple IL-32 isoforms could explain this doubt and bring us closer to using them in therapy.
Non-Invasive Monitoring for Rejection in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination
Authors: Al Jurdi Ayman , Gassen Rodrigo B. , Borges Thiago J. , Solhjou Zhabiz , Hullekes Frank E. , Lape Isadora T. , Efe Orhan , Alghamdi Areej , Patel Poojan , Choi John Y. , Mohammed Mostafa T. , Bohan Brigid , Pattanayak Vikram , Rosales Ivy , Cravedi Paolo , Kotton Camille N. , Azzi Jamil R. , Riella Leonardo V.
Published: February 2022

Introduction

Studies have shown reduced antiviral responses in kidney transplant recipients (KTRs) following SARS-CoV-2 mRNA vaccination, but data on post-vaccination alloimmune responses and antiviral responses against the Delta (B.1.617.2) variant are limited.

Materials and methods

To address this issue, we conducted a prospective, multi-center study of 58 adult KTRs receiving mRNA-BNT162b2 or mRNA-1273 vaccines. We used multiple complementary non-invasive biomarkers for rejection monitoring including serum creatinine, proteinuria, donor-derived cell-free DNA, peripheral blood gene expression profile (PBGEP), urinary CXCL9 mRNA and de novo donor-specific antibodies (DSA). Secondary outcomes included development of anti-viral immune responses against the wild-type and Delta variant of SARS-CoV-2.

Results

At a median of 85 days, no KTRs developed de novo DSAs and only one patient developed acute rejection following recent conversion to belatacept, which was associated with increased creatinine and urinary CXCL9 levels. During follow-up, there were no significant changes in proteinuria, donor-derived cell-free DNA levels or PBGEP. 36% of KTRs in our cohort developed anti-wild-type spike antibodies, 75% and 55% of whom had neutralizing responses against wild-type and Delta variants respectively. A cellular response against wild-type S1, measured by interferon-γ-ELISpot assay, developed in 38% of KTRs. Cellular responses did not differ in KTRs with or without antibody responses.

Conclusions

SARS-CoV-2 mRNA vaccination in KTRs did not elicit a significant alloimmune response. About half of KTRs who develop anti-wild-type spike antibodies after two mRNA vaccine doses have neutralizing responses against the Delta variant. There was no association between anti-viral humoral and cellular responses.
Dihydronicotinamide Riboside Is a Potent NAD+ Precursor Promoting a Pro-Inflammatory Phenotype in Macrophages
Authors: Chini Claudia C. S. , Peclat Thais R. , Gomez Lilian S. , Zeidler Julianna D. , Warner Gina M. , Kashyap Sonu , Mazdeh Delaram Z. , Hayat Faisal , Migaud Marie E. , Paulus Aneel , Chanan-Khan Asher A. , Chini Eduardo N.
Published: February 2022

Nicotinamide adenine dinucleotide (NAD) metabolism plays an important role in the regulation of immune function. However, a complete picture of how NAD, its metabolites, precursors, and metabolizing enzymes work together in regulating immune function and inflammatory diseases is still not fully understood. Surprisingly, few studies have compared the effect of different forms of vitamin B3 on cellular functions. Therefore, we investigated the role of NAD boosting in the regulation of macrophage activation and function using different NAD precursors supplementation. We compared nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and nicotinamide (NAM) supplementation, with the recently described potent NAD precursor NRH. Our results show that only NRH supplementation strongly increased NAD+ levels in both bone marrow-derived and THP-1 macrophages. Importantly, NRH supplementation activated a pro-inflammatory phenotype in resting macrophages, inducing gene expression of several cytokines, chemokines, and enzymes. NRH also potentiated the effect of lipopolysaccharide (LPS) on macrophage activation and cytokine gene expression, suggesting that potent NAD+ precursors can promote inflammation in macrophages. The effect of NRH in NAD+ boosting and gene expression was blocked by inhibitors of adenosine kinase, equilibrative nucleoside transporters (ENT), and IκB kinase (IKK). Interestingly, the IKK inhibitor, BMS-345541, blocked the mRNA expression of several enzymes and transporters involved in the NAD boosting effect of NRH, indicating that IKK is also a regulator of NAD metabolism. In conclusion, NAD precursors such as NRH may be important tools to understand the role of NAD and NADH metabolism in the inflammatory process of other immune cells, and to reprogram immune cells to a pro-inflammatory phenotype, such as the M2 to M1 switch in macrophage reprogramming, in the cancer microenvironment.
Hederasaponin C Alleviates Lipopolysaccharide-Induced Acute Lung Injury In Vivo and In Vitro Through the PIP2/NF-κB/NLRP3 Signaling Pathway
Authors: Han Shan , Yuan Renyikun , Cui Yushun , He Jia , Wang Qin-Qin , Zhuo Youqiong , Yang Shilin , Gao Hongwei
Published: February 2022

Gene transcription is governed by epigenetic regulation that is essential for the pro-inflammatory mediators surge following pathological triggers. Acute lung injury (ALI) is driven by pro-inflammatory cytokines produced by the innate immune system, which involves the nod-like receptor 3 (NLRP3) inflammasome and nuclear factor-κB (NF-κB) pathways. These two pathways are interconnected and share a common inducer the phosphatidylinositol 4,5-bisphosphate (PIP2), an epigenetic regulator of (Ribosomal ribonucleic acid (rRNA) gene transcription, to regulate inflammation by the direct inhibition of NF-κB phosphorylation and NLRP3 inflammasome activation. Herein, we report that hederasaponin C (HSC) exerted a therapeutic effect against ALI through the regulation of the PIP2/NF-κB/NLRP3 signaling pathway. In lipopolysaccharide (LPS)/lipopolysaccharide + adenosine triphosphate (LPS+ATP)-stimulated macrophages, our results showed that HSC remarkably inhibited the secretion of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α). Moreover, HSC inhibited NF-κB/p65 nuclear translocation and the binding of PIP2 to transforming growth factor-β activated kinase 1 (TAK1). The intracellular calcium (Ca2+) level was decreased by HSC via the PIP2 signaling pathway, which subsequently inhibited the activation of NLRP3 inflammasome. HSC markedly alleviated LPS-induced ALI, restored lung function of mice, and rescued ALI-induced mice death. In addition, HSC significantly reduced the level of white blood cells (WBC), neutrophils, and lymphocytes, as well as pro-inflammatory mediators like IL-6, IL-1β, and TNF-α. Hematoxylin and eosin (H&E) staining results suggested HSC has a significant therapeutic effect on lung injury of mice. Interestingly, the PIP2/NF-κB/NLRP3 signaling pathway was further confirmed by the treatment of HSC with ALI, which is consistent with the treatment of HSC with LPS/LPS+ATP-stimulated macrophages. Overall, our findings revealed that HSC demonstrated significant anti-inflammatory activity through modulating the PIP2/NF-κB/NLRP3 axis in vitro and in vivo, suggesting that HSC is a potential therapeutic agent for the clinical treatment of ALI.
The Skeleton and Biomineralization Mechanism as Part of the Innate Immune System of Stony Corals
Authors: Levy Shani , Mass Tali
Published: February 2022

Stony corals are among the most important calcifiers in the marine ecosystem as they form the coral reefs. Coral reefs have huge ecological importance as they constitute the most diverse marine ecosystem, providing a home to roughly a quarter of all marine species. In recent years, many studies have shed light on the mechanisms underlying the biomineralization processes in corals, as characterizing the calicoblast cell layer and genes involved in the formation of the calcium carbonate skeleton. In addition, considerable advancements have been made in the research field of coral immunity as characterizing genes involved in the immune response to pathogens and stressors, and the revealing of specialized immune cells, including their gene expression profile and phagocytosis capabilities. Yet, these two fields of corals research have never been integrated. Here, we discuss how the coral skeleton plays a role as the first line of defense. We integrate the knowledge from both fields and highlight genes and proteins that are related to biomineralization and might be involved in the innate immune response and help the coral deal with pathogens that penetrate its skeleton. In many organisms, the immune system has been tied to calcification. In humans, immune factors enhance ectopic calcification which causes severe diseases. Further investigation of coral immune genes which are involved in skeleton defense as well as in biomineralization might shed light on our understanding of the correlation and the interaction of both processes as well as reveal novel comprehension of how immune factors enhance calcification.
Hemocyte Clusters Defined by scRNA-Seq in Bombyx mori: In Silico Analysis of Predicted Marker Genes and Implications for Potential Functional Roles
Authors: Feng Min , Swevers Luc , Sun Jingchen
Published: February 2022

Within the hemolymph, insect hemocytes constitute a heterogeneous population of macrophage-like cells that play important roles in innate immunity, homeostasis and development. Classification of hemocytes in different subtypes by size, morphology and biochemical or immunological markers has been difficult and only in Drosophila extensive genetic analysis allowed the construction of a coherent picture of hemocyte differentiation from pro-hemocytes to granulocytes, crystal cells and plasmatocytes. However, the advent of high-throughput single cell technologies, such as single cell RNA sequencing (scRNA-seq), is bound to have a high impact on the study of hemocytes subtypes and their phenotypes in other insects for which a sophisticated genetic toolbox is not available. Instead of averaging gene expression across all cells as occurs in bulk-RNA-seq, scRNA-seq allows high-throughput and specific visualization of the differentiation status of individual cells. With scRNA-seq, interesting cell types can be identified in heterogeneous populations and direct analysis of rare cell types is possible. Next to its ability to profile the transcriptomes of individual cells in tissue samples, scRNA-seq can be used to propose marker genes that are characteristic of different hemocyte subtypes and predict their functions. In this perspective, the identities of the different marker genes that were identified by scRNA-seq analysis to define 13 distinct cell clusters of hemocytes in larvae of the silkworm, Bombyx mori, are discussed in detail. The analysis confirms the broad division of hemocytes in granulocytes, plasmatocytes, oenocytoids and perhaps spherulocytes but also reveals considerable complexity at the molecular level and highly specialized functions. In addition, predicted hemocyte marker genes in Bombyx generally show only limited convergence with the genes that are considered characteristic for hemocyte subtypes in Drosophila.
Spotted Fever in the Morphoclimatic Domains of Minas Gerais State, Brazil
Authors: de Carvalho Nunes Emília , de Moura-Martiniano Nicole Oliveira , de Lima Duré Ana Íris , de Melo Iani Felipe Campos , de Oliveira Stefan Vilges , de Mello Flávio Luis , Gazêta Gilberto Salles
Published: February 2022

In Brazil, the tick-borne rickettsiosis known as Spotted Fever (SF) has been recorded from 59% of the Federative Units, however, the knowledge of the epidemiology and dynamics of human infection remains incipient in certain areas, complicating appropriate public health actions to inform the general population and control the disease. Here, we improved the interpretation of epidemiological information of SF cases recorded for an important endemic area. A descriptive epidemiological study was carried out based on records in the SINAN (Notifiable Diseases Information System) SF case databases. Data analysis was performed using Python programming language, Pandas library and Qgis map making. To evaluate the sociodemographic, clinical, assistance, laboratory and epidemiological characteristics, simple and relative nominal values of occurrences, means and standard deviations, and molecular analyzes were performed to identify the bioagent present in biological samples collected during each case investigation. Of the 298 confirmed cases, 98 resulted in death, the number of cases increased from 2011, and the disease scenario had 32.8% lethality. Overall, 207 cases involved men, and lethality was higher in this group. The most affected age group was 30 to 59 years old. The majority of patients reported having had contact with animals such as ticks, capybara and domestic animals such as dogs and cats. The results corroborate existing studies in areas of severe SF cases in Brazil. Despite reports of SF cases from the Cerrado Biome, analyses show that serious cases occur in anthropized areas of the Atlantic Forest biome, and in a transition area between this and the Cerrado. Complex, longitudinal, multidisciplinary studies, with an eco-epidemiological focus, should be carried out to allow the construction of algorithms capable of predicting, in time and space, the risk factors associated with severe cases and deaths from SF, with the aim of avoiding their expansion.
Harvest Time Can Affect the Optimal Yield and Quality of Sea Lettuce (Ulva fenestrata) in a Sustainable Sea-Based Cultivation
Authors: Steinhagen Sophie , Enge Swantje , Cervin Gunnar , Larsson Karin , Edlund Ulrica , Schmidt Alina E. M. , Wahlström Niklas , Kollander Barbro , Pavia Henrik , Undeland Ingrid , Toth Gunilla B.
Published: February 2022

Seaweed biomass is a renewable resource with multiple applications. Sea-based cultivation of seaweeds can provide high biomass yields, low construction, operation, and maintenance costs and could offer an environmentally and economically sustainable alternative to land-based cultivations. The biochemical profile of sea-grown biomass depends on seasonal variation in environmental factors, and the optimization of harvest time is important for the quality of the produced biomass. To identify optimal harvest times of Swedish sea-based cultivated sea lettuce (Ulva fenestrata), this study monitored biomass yield, morphology, chemical composition, fertility, and biofouling at five different harvesting times in April – June 2020. The highest biomass yields (approximately 1.2 kg fw [m rope]–1) were observed in late spring (May). The number and size of holes in the thalli and the amount of fertile and fouled tissue increased with prolonged growth season, which together led to a significant decline in both biomass yield and quality during summer (June). Early spring (April) conditions were optimal for obtaining high fatty acid, protein, biochar, phenolic, and pigment contents in the biomass, whereas carbohydrate and ash content, as well as essential and non-essential elements, increased later in the growth season. Our study results show that the optimal harvest time of sea-based cultivatedU. fenestratadepends on the downstream application of the biomass and must be carefully selected to balance yield, quality, and desired biochemical contents to maximize the output of future sea-based algal cultivations in the European Northern Hemisphere.
On Single-Cell Enzyme Assays in Marine Microbial Ecology and Biogeochemistry
Authors: Traving Sachia J. , Balmonte John Paul , Seale Dan , Arnosti Carol , Glud Ronnie N. , Hallam Steven J. , Middelboe Mathias
Published: February 2022

Extracellular enzyme activity is a well-established parameter for evaluating microbial biogeochemical roles in marine ecosystems. The presence and activity of extracellular enzymes in seawater provide insights into the quality and quantity of organic matter being processed by the present microorganisms. A key challenge in our understanding of these processes is to decode the extracellular enzyme repertoire and activities of natural communities at the single-cell level. Current measurements are carried out on bulk or size-fractionated samples capturing activities of mixed populations. This approach – even with size-fractionation – cannot be used to trace enzymes back to their producers, nor distinguish the active microbial members, leading to a disconnect between measured activities and the producer cells. By targeting extracellular enzymes and resolving their activities at the single-cell level, we can investigate underlying phenotypic heterogeneity among clonal or closely related organisms, characterize enzyme kinetics under varying environmental conditions, and resolve spatio-temporal distribution of individual enzyme producers within natural communities. In this perspective piece, we discuss state-of-the-art technologies in the fields of microfluidic droplets and functional screening of prokaryotic cells for measuring enzyme activity in marine seawater samples, one cell at a time. We further elaborate on how this single-cell approach can be used to address research questions that cannot be answered with current methods, as pertinent to the enzymatic degradation of organic matter by marine microorganisms.
TIMP-1: A Circulating Biomarker for Pulmonary Hypertension Diagnosis Among Chronic Obstructive Pulmonary Disease Patients
Authors: He Wenjun , Liu Chunli , Liao Jing , Liu Fei , Lei Hui , Wei Danmei , Ruan Honglian , Kunwar Bibhav , Lu Wenju , Wang Jian , Wang Tao
Published: February 2022

Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD) and induces increased mortality among COPD patients. However, there are no blood biomarkers to identify PH in COPD. Here, we investigated whether circulating angiogenic factors and cytokines could serve as (a) biomarker (s) for COPD-PH patients. Using Angiogenesis and Cytokine proteome profile array assay, we measured the level of 36 cytokines and 55 angiogenesis-associated proteins in plasma from four COPD patients with PH (COPD-PH) and four COPD patients without PH (COPD), respectively, tissue inhibitor of metalloproteinase 1 (TIMP-1) and thrombospondin 1(TSP-1) were significantly different between the two groups. Enzyme-linked immunosorbent assay (ELISA) was applied to measured TIMP-1 and TSP-1 in a validation cohort (COPD-PH, n = 28; COPD, n = 18), and TIMP-1 was the only factor that was significantly different between COPD-PH and COPD patients (P < 0.01). Logistic regression analysis demonstrated that elevated TIMP-1 was an independent risk factor for COPD-PH [odds ratio (OR) = 1.258, 95% CI: 1.005–1.574, P < 0.05). Next, we explored the expression level and function of TIMP-1 in human pulmonary arterial smooth muscle cells (hPASMCs) exposed to cigarette smoking extract (CSE, a major etiological factor of COPD). In cultured hPASMCs, CSE treatment increased both TIMP-1 protein level and cell proliferation, and exogenous TIMP-1 (25 ng/mL) treatment inhibited CSE-induced hPASMCs proliferation. Overall, our results indicated that TIMP-1 elevation could serve as a circulating biomarker to diagnose PH among COPD patients, and TIMP-1 elevation in COPD-PH could be adaptive.
Altered Differentiation and Inflammation Profiles Contribute to Enhanced Innate Responses in Severe COPD Epithelium to Rhinovirus Infection
Authors: Guo-Parke Hong , Linden Dermot , Mousnier Aurelie , Scott Ian C. , Killick Helen , Borthwick Lee A. , Fisher Andrew J. , Weldon Sinéad , Taggart Clifford C. , Kidney Joseph C.
Published: February 2022

Background

Respiratory viral infections are closely associated with COPD exacerbations, hospitalisations, and significant morbidity and mortality. The consequences of the persisting inflammation and differentiation status in virus associated severe disease is not fully understood. The aim of this study was to evaluate barrier function, cellular architecture, the inflammatory response in severe COPD bronchial epithelium to human rhinovirus (HRV) induced pathological changes and innate immune responses.

Methods

Well-differentiated primary bronchial epithelial cells (WD-PBECs) derived from severe COPD patients and age-matched healthy controls were cultured in the air-liquid interface (ALI) model. The differentiation phenotype, epithelial barrier integrity, pathological response and cytokine secreting profile of these cultures before and after HRV infection were investigated.

Results

WD-PBECs derived from severe COPD patients showed aberrant epithelium differentiation with a decreased proportion of ciliated cells but increased numbers of club cells and goblet cells compared with healthy controls. Tight junction integrity was compromised in both cultures following HRV infection, with heightened disruptions in COPD cultures. HRV induced increased epithelial cell sloughing, apoptosis and mucus hypersecretion in COPD cultures compared with healthy controls. A Th1/Th2 imbalance and a strong interferon and pro-inflammatory cytokine response was also observed in COPD cultures, characterized by increased levels of IFNγ, IFNβ, IP-10, IL-10 and decreased TSLP and IL-13 cytokine levels prior to HRV infection. Significantly enhanced basolateral secretion of eotaxin 3, IL-6, IL-8, GM-CSF were also observed in both mock and HRV infected COPD cultures compared with corresponding healthy controls. In response to HRV infection, all cultures displayed elevated levels of IFNλ1 (IL-29), IP-10 and TNFα compared with mock infected cultures. Interestingly, HRV infection dramatically reduced IFNλ levels in COPD cultures compared with healthy subjects.

Conclusion

An altered differentiation phenotype and cytokine response as seen in severe COPD WD-PBECs may contribute to increased disease susceptibility and an enhanced inflammatory response to HRV infection.
Early Antiretroviral Therapy in AIDS Patients Presenting With Toxoplasma gondii Encephalitis Is Associated With More Sequelae but Not Increased Mortality
Authors: Cubas-Vega Nadia , López Del-Tejo Paola , Baia-da-Silva Djane C. , Sampaio Vanderson Souza , Jardim Bruno Araújo , Santana Monique Freire , Lima Ferreira Luiz Carlos , Safe Izabella Picinin , Alexandre Márcia A. Araújo , Lacerda Marcus Vinícius Guimarães , Monteiro Wuelton Marcelo , Val Fernando
Published: February 2022

Background

Evidence on the optimal time to initiate antiretroviral therapy (ART) in the presence of toxoplasmic encephalitis (TE) is scarce. We compared the impact of early vs. delayed ART initiation on mortality and neurologic complications at discharge in a Brazilian population co-infected with HIV and TE.

Methods

We retrospectively evaluated data from 9 years of hospitalizations at a referral center in Manaus, Amazonas. All ART-naïve hospitalized patients were divided into early initiation treatment (EIT) (0-4 weeks) and delayed initiation treatment (DIT) (>4 weeks). The groups were compared using chi-square test and mortality at 16 weeks.

Results

Four hundred sixty nine patients were included, of whom 357 (76.1%) belonged to the EIT group. The median CD4+ lymphocyte count and CD4+/CD8+ ratio were 53 cells/mm3 and 0.09, respectively. Mortality rate and presence of sequelae were 4.9% (n = 23) and 41.6% (n = 195), respectively. Mortality was similar between groups (p = 0.18), although the EIT group had the highest prevalence of sequelae at discharge (p = 0.04). The hazard ratio for death at 16 weeks with DIT was 2.3 (p = 0.18). The necessity for intensive care unit admission, mechanical ventilation, and cardiopulmonary resuscitation were similar between groups.

Conclusion

In patients with AIDS and TE, early ART initiation might have a detrimental influence on the occurrence of sequelae.
Corneal Biomechanics Differences Between Chinese and Caucasian Healthy Subjects
Authors: Vinciguerra Riccardo , Herber Robert , Wang Yan , Zhang Fengju , Zhou Xingtao , Bai Ji , Yu Keming , Chen Shihao , Fang Xuejun , Raiskup Frederik , Vinciguerra Paolo
Published: February 2022

Purpose

The aim of this study was to evaluate the difference between Caucasian and Chinese healthy subjects with regards to Corvis ST dynamic corneal response parameters (DCRs).

Methods

Two thousand eight hundred and eighty-nine healthy Caucasian and Chinese subjects were included in this multicenter retrospective study. Subsequently, Chinese eyes were matched to Caucasians by age, intraocular pressure (IOP), and Corneal Thickness (CCT) using a case-control matching algorithm. The DCRs assessed were Deformation Amplitude (DA) Applanation 1 velocity (A1v), integrated radius (1/R), deformation amplitude ratio (DAratio), stiffness parameter at applanation 1 (SPA1), ARTh (Ambrósio's Relational Thickness to the horizontal profile), and the novel Stress Strain Index (SSI).

Results

After age-, CCT-, and IOP- matching, 503 Chinese were assigned to 452 Caucasians participants. Statistical analysis showed a statistical significant difference between Chinese and Caucasian Healthy subjects in the values of SPA1 (p = 0.008), Arth (p = 0.008), and SSI (p < 0.001). Conversely, DA, A1v, DAratio, and 1/R were not significantly different between the two ethnical groups (p > 0.05).

Conclusion

We found significant differences in the values of the DCRs provided by the Corvis ST between Chinese and Caucasian healthy subjects.
Risk Factors for Mortality in Abdominal Infection Patients in ICU: A Retrospective Study From 2011 to 2018
Authors: Luo Xingzheng , Li Lulan , Ou Shuhua , Zeng Zhenhua , Chen Zhongqing
Published: February 2022

To identify the risk factors related to the patient's 28-day mortality, we retrospectively reviewed the records of patients with intra-abdominal infections admitted to the ICU of Nanfang Hospital, Southern Medical University from 2011 to 2018. Multivariate Cox proportional hazard regression analysis was used to identify independent risk factors for mortality. Four hundred and thirty-one patients with intra-abdominal infections were analyzed in the study. The 28-day mortality stepwise increased with greater severity of disease expression: 3.5% in infected patients without sepsis, 7.6% in septic patients, and 30.9% in patients with septic shock (p < 0.001). In multivariate analysis, independent risk factors for 28-day mortality were underlying chronic diseases (adjusted HR 3.137, 95% CI 1.425–6.906), high Sequential Organ Failure Assessment (SOFA) score (adjusted HR 1.285, 95% CI 1.160–1.424), low hematocrit (adjusted HR 1.099, 95% CI 1.042–1.161), and receiving more fluid within 72 h (adjusted HR 1.028, 95% CI 1.015–1.041). Compared to the first and last 4 years, the early use of antibiotics, the optimization of IAT strategies, and the restriction of positive fluid balance were related to the decline in mortality of IAIs in the later period. Therefore, underlying chronic diseases, high SOFA score, low hematocrit, and receiving more fluid within 72 h after ICU admission were independent risk factors for patients' poor prognosis.
The Impact of Instant Coffee and Decaffeinated Coffee on the Gut Microbiota and Depression-Like Behaviors of Sleep-Deprived Rats
Authors: Gu Xinyi , Zhang Shuyi , Ma Weini , Wang Qixue , Li Ying , Xia Chenyi , Xu Ying , Zhang Ting , Yang Li , Zhou Mingmei
Published: February 2022

Objective

Based on our previous research, chronic paradoxical sleep deprivation (PSD) can cause depression-like behaviors and microbial changes in gut microbiota. Coffee, as the world’s most popular drink for the lack of sleep, is beneficial to health and attention and can eliminate the cognitive sequelae caused by poor sleep. The purpose of this study is to investigate the effects of coffee and decaffeinated coffee on PSD rats.

Research Design and Methods

A total of 32 rats were divided into four groups: control group, PSD model group, conventional coffee group, and decaffeinated coffee group. Behavioral tests, including sucrose preference test, open field test, forced swimming test, and tail suspension test, as well as biochemical detection for inflammatory and antioxidant indexes were performed. The effects of coffee and decaffeinated coffee on the gut microbiota of PSD rats were investigated by 16S rRNA gene sequencing.

Results

Coffee and decaffeinated coffee significantly improved the depression-like behaviors. Moreover, the serum levels of interleukin-6 and tumor necrosis factor alpha were decreased in both coffee and decaffeinated coffee groups, as well as the levels of superoxide dismutase and GSH-Px were increased. Gut microbiota analysis revealed that the abundance of S24-7, Lachnospiraceae, Oscillospira, and Parabacteroides were significantly increased in PSD rats, while the abundance of Akkermansia and Klebsiella were significantly decreased. After the treatment of coffee and decaffeinated coffee, the abundance of the above gut microbiota was all restored in different degrees. Coffee had relatively more significant effects on PSD-induced depressive-like behaviors, while the difference between coffee and decaffeinated coffee was not obvious in correcting the disorder of gut microbiota.

Conclusions

These findings have shown that both coffee and decaffeinated coffee are effective for sleep deprivation-induced depression-like behaviors and the dysbiosis of gut microbiota and indicated that caffeine may be not the only key substance of coffee for regulating gut microbiota.
Oxytetracycline and Streptomycin Resistance Genes in Xanthomonas arboricola pv. pruni, the Causal Agent of Bacterial Spot in Peach
Authors: Herbert Austin , Hancock C. Nathan , Cox Brodie , Schnabel Guido , Moreno Daniela , Carvalho Renato , Jones Jeffrey , Paret Matthew , Geng Xueqing , Wang Hehe
Published: February 2022

Xanthomonas arboricola pv. pruni (Xap) causes bacterial spot, a major worldwide disease of Prunus species. Very few chemical management options are available for this disease and frequent applications of oxytetracycline (OTC) in the United States peach orchards have raised concerns about resistance development. During 2017–2020, 430 Xap strains were collected from ten peach orchards in South Carolina. Seven OTC-resistant (OTCR) Xap strains were found in 2017 and 2020 from four orchards about 20–270 km apart. Interestingly, the seven strains were also resistant to streptomycin (STR). Six strains grew on media amended with ≤100 μg/mL OTC, while one strain, R1, grew on ≤250 μg/mL OTC. Genome sequence analysis of four representative OTCR strains revealed a 14–20 kb plasmid carrying tetC, tetR, and strAB in each strain. These three genes were transferable to Xanthomonas perforans via conjugation, and they were PCR confirmed in all seven OTCR Xap strains. When tetC and tetR were cloned and expressed together in a sensitive strain, the transconjugants showed resistance to ≤100 μg/mL OTC. When tetC was cloned and expressed alone in a sensitive strain, the transconjugants showed resistance to ≤250 μg/mL OTC. TetC and tetR expression was inducible by OTC in all six wild-type strains resistant to ≤100 μg/mL OTC. However, in the R1 strain resistant to ≤250 μg/mL OTC, tetR was not expressed, possibly due to the presence of Tn3 in the tetR gene, and in this case tetC was constitutively expressed. These data suggest that tetC confers OTC resistance in Xap strains, and tetR regulates the level of OTC resistance conferred by tetC. To our knowledge, this is the first report of OTC resistance in plant pathogenic xanthomonads.
The Combined Use of Pediococcus pentosaceus and Fructooligosaccharide Improves Growth Performance, Immune Response, and Resistance of Whiteleg Shrimp Litopenaeus vannamei Against Vibrio parahaemolyticus
Authors: Hong Nguyen Thi Xuan , Linh Nguyen Thi Hue , Baruah Kartik , Thuy Do Thi Bich , Phuoc Nguyen Ngoc
Published: February 2022

In this study, we evaluated the effect of probiotic bacteria Pediococcus pentosaceus supplemented at different inclusion levels in a control diet [basal diet containing 0.5% fructooligosaccharide (FOS)] on the growth performance, feed conversion ratio, immune response, and the disease resistance of whiteleg shrimp Litopenaeus vannamei juveniles against Vibrio parahaemolyticus. A control diet with 0.5% FOS but without P. pentosaceus supplementation (Control) was prepared. In addition, three other test diets were also formulated: control diet supplemented with P. pentosaceus at (i) 1 × 106 cfu g–1 diet (P1), (ii) 1 × 107 cfu g–1 diet (P2), or (iii) 1 × 108 cfu g–1 diet (P3). After a 60-day feeding trial, the experimental shrimps were challenged with V. parahaemolyticus. The results showed that dietary supplementation of P. pentosaceus significantly improved the growth performance and immune responses of L. vannamei juveniles. The juveniles that were fed with a P2 or P3 diet recorded the maximum increase in the final body weight, final length, weight gain, and survival rate. The total hemocyte counts, phenoloxidase, and lysozyme activity of shrimp fed with either of these two diets were significantly enhanced. The results also showed that juveniles fed with a P2 or P3 diet exhibited significantly lower mortality when challenged with V. parahaemolyticus. Overall results suggested that a combination of P. pentosaceus at the inclusion level of 1 × 107 cfu g–1 diet (P2) and 0.5% FOS could be considered as a potential synbiotic formulation for improving the growth, health, and robustness of L. vannamei.
Influence of Dairy Cows Bedding Material on the Microbial Structure and Antibiotic Resistance Genes of Milk
Authors: Wu Haoming , Wang Yang , Du Bingyao , Li Huiying , Dong Lei , Hu Haiyan , Meng Lu , Zheng Nan , Wang Jiaqi
Published: February 2022

The presence of pathogenic bacteria and antibiotic resistance genes (ARGs) in milk are among the most important issues related to the safety of dairy products and the health of consumers. However, despite that dairy cow are housed for long periods of time on different beddings, the effect of different bedding materials on the microbiota and presence of ARGs is unclear. In this study, the composition of microorganisms, and the presence of mastitis pathogens and 33 ARGs targeting seven antibiotics in raw milk produced from farms using sand bedding, rice husk bedding, and recycled manure solids (RMS) bedding were compared by amplicon sequencing and real-time quantitative PCR. The results showed that the microbial composition of milk was related to the microbiota of bedding. None of the mastitis pathogens were detected in milk from cows housed on sand bedding (S-M). The proportion of ARGs was highest in the S-M group and lowest in the milk from cows housed on RMS bedding (RMS-M) group. In general, the content of ARGs in RMS-M was the lowest, however, the RMS bedding may pose a threat to the breast health of dairy cows.
The Small RNA Universe of Capitella teleta
Authors: Khanal Sweta , Zancanela Beatriz Schueng , Peter Jacob Oche , Flynt Alex Sutton
Published: February 2022

RNAi is an evolutionarily fluid mechanism with dramatically different activities across animal phyla. One major group where there has been little investigation is annelid worms. Here, the small RNAs of the polychaete developmental model Capitella teleta are profiled across development. As is seen with nearly all animals, nearly 200 microRNAs were found with 58 high-confidence novel species. Greater miRNA diversity was associated with later stages consistent with differentiation of tissues. Outside miRNA, a distinct composition of other small RNA pathways was found. Unlike many invertebrates, an endogenous siRNA pathway was not observed, indicating pathway loss relative to basal planarians. No processively generated siRNA-class RNAs could be found arising from dsRNA precursors. This has a significant impact on RNAi technology development for this group of animals. Unlike the apparent absence of siRNAs, a significant population of piRNAs was observed. For many piRNAs, phasing and ping-pong biogenesis pathways were identified. Interestingly, piRNAs were found to be highly expressed during early development, suggesting a potential role in regulation in metamorphosis. Critically, the configuration of RNAi factors in C. teleta is found in other annelids and mollusks, suggesting that similar biology is likely to be present in the wider clade. This study is the first in providing comprehensive analysis of small RNAs in annelids.
Human Sulfotransferase Assays With PAPS Production in situ
Authors: Sun Yanan , Harps Lukas Corbinian , Bureik Matthias , Parr Maria Kristina
Published: February 2022

For in vitro investigations on human sulfotransferase (SULT) catalyzed phase II metabolism, the costly cofactor 3′-phosphoadenosine-5′-phosphosulfate (PAPS) is generally needed. In the present study, we developed and optimized a new approach that combines SULT-dependent biotransformation using recombinant and permeabilized fission yeast cells (enzyme bags) with PAPS production in situ applying quality by design principles. In the initial application of the procedure, yeast cells expressing human SULT1A3 were used for the production of 4′-hydroxypropranolol-4-O-sulfate from 4-hydroxypropranolol. The optimized protocol was then successfully transferred to other sulfonation reactions catalyzed by SULT2A1, SULT1E1, or SULT1B1. The concomitant degradation of some sulfoconjugates was investigated, and further optimization of the reaction conditions was performed in order to reduce product loss. Also, the production of stable isotope labelled sulfoconjugates was demonstrated utilizing isotopically labelled substrates or 34S-sulfate. Overall, this new approach results in higher space-time yields while at the same time reducing experimental cost.
Endoglin Wild Type and Variants Associated With Hereditary Hemorrhagic Telangiectasia Type 1 Undergo Distinct Cellular Degradation Pathways
Authors: Gariballa Nesrin , Kizhakkedath Praseetha , Akawi Nadia , John Anne , Ali Bassam R.
Published: February 2022

Endoglin, also known as cluster of differentiation 105 (CD105), is an auxiliary receptor in the TGFβ signaling pathway. It is predominantly expressed in endothelial cells as a component of the heterotetrameric receptor dimers comprising type I, type II receptors and the binding ligands. Mutations in the gene encoding Endoglin (ENG) have been associated with hereditary hemorrhagic telangiectasia type 1 (HHT1), an autosomal dominant inherited disease that is generally characterized by vascular malformation. Secretory and many endomembrane proteins synthesized in the Endoplasmic reticulum (ER) are subjected to stringent quality control mechanisms to ensure that only properly folded and assembled proteins are trafficked forward through the secretory pathway to their sites of action. We have previously demonstrated that some Endoglin variants causing HHT1 are trapped in the ER and fail to traffic to their normal localization in plasma membrane, which suggested the possible involvement of ER associated protein degradation (ERAD) in their molecular pathology. In this study, we have investigated, for the first time, the degradation routes of Endoglin wild type and two mutant variants, P165L and V105D, and previously shown to be retained in the ER. Stably transfected HEK293 cells were treated with proteasomal and lysosomal inhibitors in order to elucidate the exact molecular mechanisms underlying the loss of function phenotype associated with these variants. Our results have shown that wild type Endoglin has a relatively short half-life of less than 2 hours and degrades through both the lysosomal and proteasomal pathways, whereas the two mutant disease-causing variants show high stability and predominantly degrades through the proteasomal pathway. Furthermore, we have demonstrated that Endoglin variants P165L and V105D are significantly accumulated in HEK293 cells deficient in HRD1 E3 ubiquitin ligase; a major ERAD component. These results implicate the ERAD mechanism in the pathology of HHT1 caused by the two variants. It is expected that these results will pave the way for more in-depth research studies that could provide new windows for future therapeutic interventions.
Inhibitors of Human Neuraminidase Enzymes Block Transmigration in vitro
Authors: Howlader Md. Amran , Guo Tianlin , Cairo Christopher W.
Published: February 2022

Cell migration to a site of inflammation is an important step of the immune response. This process is coordinated by cytokines, receptors, and the signal processing machinery of the cell. Many cellular receptors are glycosylated, and their activity can be modulated through changes in glycan structure. Furthermore, glycosylation can be critical to the folding and trafficking of receptors. In this work, we investigated the role of native human neuraminidase enzymes (NEU) in transmigration. We used a cultured T cell line (Jurkat) and a transwell assay with fibronectin (FN) coated wells and cytokines (IL-4 and TNF-α) as chemoattractants in the bottom chamber. We observed that NEU1, NEU3, and NEU4 were positive regulators of transmigration using an siRNA knockdown. Furthermore, we found that pharmacological inhibition of these enzymes inhibited transmigration. We conclude that human NEU isoenzymes NEU1, NEU3, and NEU4 can act as positive regulators of transmigration and should be investigated as targets for anti-inflammatory strategies.
Insights on Human Small Heat Shock Proteins and Their Alterations in Diseases
Authors: Tedesco B. , Cristofani R. , Ferrari V. , Cozzi M. , Rusmini P. , Casarotto E. , Chierichetti M. , Mina F. , Galbiati M. , Piccolella M. , Crippa V. , Poletti A.
Published: February 2022

The family of the human small Heat Shock Proteins (HSPBs) consists of ten members of chaperones (HSPB1-HSPB10), characterized by a low molecular weight and capable of dimerization and oligomerization forming large homo- or hetero-complexes. All HSPBs possess a highly conserved centrally located α-crystallin domain and poorly conserved N- and C-terminal domains. The main feature of HSPBs is to exert cytoprotective functions by preserving proteostasis, assuring the structural maintenance of the cytoskeleton and acting in response to cellular stresses and apoptosis. HSPBs take part in cell homeostasis by acting as holdases, which is the ability to interact with a substrate preventing its aggregation. In addition, HSPBs cooperate in substrates refolding driven by other chaperones or, alternatively, promote substrate routing to degradation. Notably, while some HSPBs are ubiquitously expressed, others show peculiar tissue-specific expression. Cardiac muscle, skeletal muscle and neurons show high expression levels for a wide variety of HSPBs. Indeed, most of the mutations identified in HSPBs are associated to cardiomyopathies, myopathies, and motor neuropathies. Instead, mutations in HSPB4 and HSPB5, which are also expressed in lens, have been associated with cataract. Mutations of HSPBs family members encompass base substitutions, insertions, and deletions, resulting in single amino acid substitutions or in the generation of truncated or elongated proteins. This review will provide an updated overview of disease-related mutations in HSPBs focusing on the structural and biochemical effects of mutations and their functional consequences.
Inhibition of Protein Kinase CK2 Affects Thymidylate Synthesis Cycle Enzyme Level and Distribution in Human Cancer Cells
Authors: Wińska Patrycja , Widło Łukasz , Senkara Elżbieta , Koronkiewicz Mirosława , Cieśla Jarosław M. , Krzyśko Alicja , Skierka Katarzyna , Cieśla Joanna
Published: February 2022

Thymidylate synthase (TS), dihydrofolate reductase (DHFR), and serine hydroxymethyltransferase (SHMT) constitute the thymidylate synthesis cycle providing thymidylate for DNA synthesis and repair. Our previous studies indicated that TS and DHFR are the substrates of protein kinase CK2. This work has been aimed at the elucidation of the effect of CK2 activity on cell cycle progression, thymidylate synthesis enzyme expression and localization, and the role of CK2-mediated TS phosphorylation in in vitro di- and trimolecular complex formation. The results were obtained by means of western blot, confocal microscopy, flow cytometry, quantitative polymerase chain reaction (QPCR), quartz crystal microbalance with dissipation monitoring (QCM-D), and microthermophoresis (MST). Our research indicates that CK2 inhibition does not change the levels of the transcripts; however, it affects the protein levels of DHFR and TS in both tested cell lines, i.e., A549 and CCRF-CEM, and the level of SHMT1 in CCRF-CEM cells. Moreover, we show that CK2-mediated phosphorylation of TS enables the protein (pTS) interaction with SHMT1 and leads to the stability of the tri-complex containing SHMT1, DHFR, and pTS. Our results suggest an important regulatory role of CK2-mediated phosphorylation for inter- and intracellular protein level of enzymes involved in the thymidylate biosynthesis cycle.