bluuebunny/crossref_metadata_2025 huggingface dataset:
PTRH2 Gene Variants: Recent Review of the Phenotypic Features and Their Bioinformatics Analysis
Authors: Sharkia Rajech , Jain Sahil , Mahajnah Muhammad , Habib Clair , Azem Abdussalam , Al-Shareef Wasif , Zalan Abdelnaser
Published: May 2023

Peptidyl-tRNA hydrolase 2 (PTRH2) is an evolutionarily highly conserved mitochondrial protein. The biallelic mutations in the PTRH2 gene have been suggested to cause a rare autosomal recessive disorder characterized by an infantile-onset multisystem neurologic endocrine and pancreatic disease (IMNEPD). Patients with IMNEPD present varying clinical manifestations, including global developmental delay associated with microcephaly, growth retardation, progressive ataxia, distal muscle weakness with ankle contractures, demyelinating sensorimotor neuropathy, sensorineural hearing loss, and abnormalities of thyroid, pancreas, and liver. In the current study, we conducted an extensive literature review with an emphasis on the variable clinical spectrum and genotypes in patients. Additionally, we reported on a new case with a previously documented mutation. A bioinformatics analysis of the various PTRH2 gene variants was also carried out from a structural perspective. It appears that the most common clinical characteristics among all patients include motor delay (92%), neuropathy (90%), distal weakness (86.4%), intellectual disability (84%), hearing impairment (80%), ataxia (79%), and deformity of head and face (~70%). The less common characteristics include hand deformity (64%), cerebellar atrophy/hypoplasia (47%), and pancreatic abnormality (35%), while the least common appear to be diabetes mellitus (~30%), liver abnormality (~22%), and hypothyroidism (16%). Three missense mutations were revealed in the PTRH2 gene, the most common one being Q85P, which was shared by four different Arab communities and was presented in our new case. Moreover, four different nonsense mutations in the PTRH2 gene were detected. It may be concluded that disease severity depends on the PTRH2 gene variant, as most of the clinical features are manifested by nonsense mutations, while only the common features are presented by missense mutations. A bioinformatics analysis of the various PTRH2 gene variants also suggested the mutations to be deleterious, as they seem to disrupt the structural confirmation of the enzyme, leading to loss of stability and functionality.
Efficacy of Health Promotion Interventions Aimed to Improve Health Gains in Middle-Aged Adults—A Systematic Review
Authors: Santos Eunice M. C. P. , Canhestro Ana M. G. D. S. , Rosário Jorge M. O. A. , Fonseca César J. V. , Pinho Lara M. G. , Arco Helena M. S. L. R.
Published: May 2023

Population aging will be one of the major social transformations in the coming decades, with a very significant impact in all countries. The consequences of this will cause an overload of social and health services. It will be necessary to prepare for an aging population. The promotion of healthy lifestyles is necessary to increase quality of life and well-being as people age. The aim of this study was to identify and synthesize interventions in middle-aged adults that promote healthy lifestyles and translate this knowledge into health gains. We performed a systematic review of the literature with research on the EBSCO Host—Research Databases platform. The methodology followed the PRISMA guidelines, and the protocol was registered with PROSPERO. A total of 10 articles out of 44 retrieved were included in this review, which identified interventions to promote healthy lifestyles with an impact on well-being, quality of life, and adherence to healthy behaviors. The synthesized evidence supports the efficacy of interventions that contributed to positive changes at the biopsychosocial level. Health promotion interventions were educational or motivational and related to physical exercise, healthy eating, and changes in habits and lifestyles related to harmful behaviors (tobacco use, excess carbohydrates in the diet, physical inactivity, and stress). The health gains found were increased mental health knowledge (self-actualization), adherence to physical exercise, improvement in physical condition, adherence to the consumption of fruits and vegetables, increased quality of life, and well-being. Health promotion interventions in middle-aged adults can significantly improve healthy lifestyles, protecting them from the negative effect of aging. For aging to be a successful experience, continuity of healthy lifestyles practiced in middle age is necessary.
Effective Priming Techniques to Enhance Ghaf (Prosopis cineraria L. Druce) Seed Germination for Mass Planting
Authors: Hassan Fatima E. , Alyafei Mohammed A. S. , Kurup Shyam , Jaleel Abdul , Al Busaidi Nabra , Ahmed Zienab F. R.
Published: May 2023

Seed priming is a cost-effective and efficient pre-sowing technique that promotes seed germination and plant growth under abiotic stress. This study was conducted to investigate the effect of different priming treatments on breaking the dormancy of ghaf (Prosopis cineraria L. Druce) seeds. Furthermore, the effects of storage conditions and seed coating on seed germination were examined. Treatments with hot water, KNO3, KCl, polyethylene glycol (PEG), H2SO4, gibberellin (GA3), cytokinin benzyl adenine (BA), and H2SO4 + BA were investigated. Among all the tested treatments, seeds responded the best to the H2SO4 50% 2 min + BA (200 ppm) priming treatment in terms of germination uniformity and effectiveness. This treatment initiated germination 5 days after sowing and increased the germination percentage from 11.32% in the untreated seed to 83% and 100% in the primed ones after 5 and 20 days, respectively. The germination percentage and primary root length were shown to be more responsive to this combined treatment, followed by the H2SO4 50% 2 min+ BA 100 ppm. This treatment achieved the best result of 100% germination when the seeds were covered in a seed ball. Additionally, the treated seeds could be stored at room temperature or 4 °C for more than 10 days with no negative effect on the germination. Based on these findings, this treatment could be recommended to farmers and plant producers to boost the mass production of ghaf trees.
The Dormancy Types and Germination Characteristics of the Seeds of Berberis koreana Palibin, an Endemic Species of Korea
Authors: Kim Do-Hyun , Kim Sang-Geun , Lee Hayan , Na Chae-Sun , Lee Do-Hyung
Published: May 2023

Berberis koreana Palibin is an endemic plant native to Korea. In this study, we aimed to study the seed germination of this species using a water imbibition experiment, gibberellic acid (GA3) treatment (0, 10, 100, or 1000 mg·L−1), cold stratification (0, 2, 4, 8, or 12 weeks at 4 °C), move-along experiment, and phenology studies. In the water imbibition experiment, the weight of the seeds increased by more than 120% in 24 h. An analysis of the internal and external morphological characteristics of the seed revealed that the embryo was already fully grown from the fruit and did not grow thereafter. The final germination percentages for the cold stratification at 0, 2, 4, 8, and 12 weeks at 4 °C were 12 ± 3.65, 32 ± 9.09, 59 ± 1.00, 59 ± 9.59, and 71 ± 1.91%, respectively. In the move-along experiment and phenology studies, a longer low-temperature treatment period resulted in a higher germination percentage. However, the GA3 treatment had little effect on the seed germination. Our results indicate that B. koreana exhibits an intermediate physiological seed dormancy.
Experiences of Self-Stigma in People with Chronic Psychosis: A Qualitative Study
Authors: Arboleya-Faedo Tatiana , González-Menéndez Ana , González-Pando David , Paino Mercedes , Alonso-Pérez Fernando
Published: May 2023

We present the results of a phenomenological study understanding the personal meaning of self-stigma in people with chronic psychosis. Self-stigma is a frequent phenomenon in the lives of people with psychosis and their families and it functions as a barrier to recovery. Semi-structured in-depth interviews were conducted with fourteen outpatients that suffer from chronic psychosis during January 2020. Data analysis was carried out using an inductive approach as described by Graneheim and Lundman through the MAXQDA 2022 program. The themes observed were: “Contextual Stigma”, “Components of Self-Stigma”, “Skills Loss” and “Coping with Self-Stigma”. The main categories and subcategories were avoidance and escape behaviours from their social environment, labelling, loss of social relationships, negative impact and self-concealment of the diagnosis. Our results revealed influence on each other, forming a looping effect that explains and amplifies the lived experience of self-stigma. These findings highlight the need to implement strategies in nursing practice aimed at training the acceptance and distancing necessary to minimize the impact of self-stigma on people with chronic psychosis. This study adheres to the EQUATOR guidelines for the Consolidated Criteria for Reporting Qualitative Research (COREQ).
Race and Ethnicity Misclassification in Hospital Discharge Data and the Impact on Differences in Severe Maternal Morbidity Rates in Florida
Authors: Reid Chinyere N. , Obure Renice , Salemi Jason L. , Ilonzo Chinwendu , Louis Judette , Rubio Estefania , Sappenfield William M.
Published: May 2023

Hospital discharge (HD) records contain important information that is used in public health and health care sectors. It is becoming increasingly common to rely mostly or exclusively on HD data to assess and monitor severe maternal morbidity (SMM) overall and by sociodemographic characteristics, including race and ethnicity. Limited studies have validated race and ethnicity in HD or provided estimates on the impact of assessing health differences in maternity populations. This study aims to determine the differences in race and ethnicity reporting between HD and birth certificate (BC) data for maternity hospitals in Florida and to estimate the impact of race and ethnicity misclassification on state- and hospital-specific SMM rates. We conducted a population-based retrospective study of live births using linked BC and HD records from 2016 to 2019 (n = 783,753). BC data were used as the gold standard. Race and ethnicity were categorized as non-Hispanic (NH)-White, NH-Black, Hispanic, NH-Asian Pacific Islander (API), and NH-American Indian or Alaskan Native (AIAN). Overall, race and ethnicity misclassification and its impact on SMM at the state- and hospital levels were estimated. At the state level, NH-AIAN women were the most misclassified (sensitivity: 28.2%; positive predictive value (PPV): 25.2%) and were commonly classified as NH-API (30.3%) in HD records. NH-API women were the next most misclassified (sensitivity: 57.3%; PPV: 85.4%) and were commonly classified as NH-White (5.8%) or NH-other (5.5%). At the hospital level, wide variation in sensitivity and PPV with negative skewing was identified, particularly for NH-White, Hispanic, and NH-API women. Misclassification did not result in large differences in SMM rates at the state level for all race and ethnicity categories except for NH-AIAN women (% difference 78.7). However, at the hospital level, Hispanic women had wide variability of a percent difference in SMM rates and were more likely to have underestimated SMM rates. Reducing race and ethnicity misclassification on HD records is key in assessing and addressing SMM differences and better informing surveillance, research, and quality improvement efforts.
The Relationship between Mindfulness and Readiness to Change in Alcohol Drinkers
Authors: Abo Hamza Eid , Yoon Adam , Liu Liquan , Garg Anchal , Richard Yuliya , Frydecka Dorota , Helal Ahmed , Moustafa Ahmed A.
Published: May 2023

Mindfulness is a multi-faceted construct that involves paying attention to thoughts and emotions without automatically reacting and being critical of them. Recent research has suggested that mindfulness might play an important role in reducing problematic alcohol use. Further, Readiness to Change (RTC) is related to motivation to change drinking behaviours. The RTC scale identifies motivation to change drinking behaviours including Precontemplation, Contemplation, and Action stages. The current study investigated, for the first time, the relationship between mindfulness (and its facets) and RTC in relation to drinking behaviours. Undergraduate students from Western Sydney University (N = 279) were screened for drinking levels using the Alcohol Use Disorder Identification Test (AUDIT) and then completed the Readiness to Change Questionnaire (RCT) and the Five Facets Mindfulness Questionnaire (FFMQ), which includes the following facets: Acting with Awareness, Non-Judging of Inner Experience, Non-Reactivity to Inner Experience, Describing, and Observing. Results show that overall, mindfulness and its facets negatively correlated with RTC. Multiple regression analysis further showed that Awareness and Non-Judgement facets negatively predicted RTC. These findings provide insight into how the facets of mindfulness interact with the drinking motives of individuals and their intentions to change drinking behaviours. Based on these findings, we recommend the incorporation of mindfulness techniques in interventions targeting problematic drinking.
Influence of Age on Associations of Occlusal Status and Number of Present Teeth with Dementia in Community-Dwelling Older People in Japan: Cross-Sectional Study
Authors: Shiraki Hikaru , Kakuta Satoko , Park Ji-Woo , Aosa Taishi , Ansai Toshihiro
Published: May 2023

While occlusal status has been reported to be related to cognitive function, little is known about the influence of age on that relationship. The present study examined the associations of tooth loss and occlusal status with dementia in the older people, as well as the effects of age on those relationships. A total of 196 older participants (median age: 84 years) were enrolled. Occlusal status was assessed using functional tooth units (FTU), calculated based on the number of paired natural or artificial teeth. Logistic regression analysis was then performed using dementia as the objective variable, and FTU or number of teeth as explanatory variables. The results showed that higher FTU was associated with lower risk of dementia. Furthermore, when stratified by median age, the association was greater for those aged less than 84 years. On the other hand, there was no significant association of number of present teeth with dementia. These results suggest that the risk of dementia is lower for individuals with better occlusion and that occlusal factor may have a greater effect on dementia onset in younger older people. It is thus recommended that both occlusal function and age be incorporated as factors in programs developed for dementia prevention.
Social, Geographical and Income Inequality as Demonstrated by the Coronary Calcium Score: An Ecological Study in Sydney, Australia
Authors: Coorey Craig Peter , Knibbs Luke D. , Otton James
Published: May 2023

Background: The coronary calcium score is a non-invasive biomarker of coronary artery disease. The concept of “arterial age” transforms the coronary calcium score to an expected age based on the degree of coronary atherosclerosis. This study aimed to investigate the relationship of socioeconomic status with the burden of coronary artery disease within Sydney, Australia. Methods: This was an ecological study at the postcode level of patients aged 45 and above who had completed a CT coronary calcium scan within New South Wales (NSW), Australia from January 2012 to December 2020. Arterial age difference was calculated as arterial age minus chronological age. Socioeconomic data was obtained for median income, Index of Relative Socio-economic Advantage and Disadvantage (IRSAD) score and median property price. Linear regression was used for analysis. Results: There were 17,102 patients across 325 postcodes within NSW, comprising 9129 males with a median arterial age difference of 7 years and 7972 females with -9 years. Income, IRSAD score and property price each had an inverse relationship with arterial age difference (p-values < 0.05). Conclusions: Income, socioeconomic status and local property prices are significantly correlated with premature coronary aging. Healthcare resource allocation and prevention should target the inequalities identified to reduce the burden of coronary artery disease.
Framing a New Nutrition Policy: Changes on Key Stakeholder’s Discourses throughout the Implementation of the Chilean Food Labelling Law
Authors: Mediano Fernanda , Fierro Camila , Corvalán Camila , Reyes Marcela , Correa Teresa
Published: May 2023

The global implementation of structural policies to tackle obesity has been slow, likely because of the competing interests of governments and the food industry. We used the discussion of the Chilean Food Labeling Law to identify influential stakeholders in the media and their frames during different periods of the law’s implementation. This involved a content analysis of the food regulation media coverage in five key periods from 2007, when the food bill was first introduced in Congress, to 2018, when the second phase of the law was implemented (N = 1295). We found that most of the law coverage was through elite press. Half of the sources were from the food industry (26.7%) and government (26.2%), while other stakeholders, were less prevalent. Frames were mostly competing, except for cooperation with the law. The main food industry frame used during the discussion of the law was the “economic threat” (41.9%), whose prevalence decreased at the post-implementation period (13%, p < 0.01). No other relevant stakeholders changed their framing. Our results highlight that there are several aspects of public health communication, such as the type of media used, the involvement of scholars and civil society, and the framing, that could be improved to advance food environment policies.
The Impact of Social Loafing on Turnover Intention for Tourism Employees Post COVID-19: The Mediating Role of Mental Health
Authors: Elshaer Ibrahim A. , Algezawy Mohamed , Ghaleb Mohanad M. S. , Mohamed Shaimaa A. , Azazz Alaa M. S.
Published: May 2023

The COVID-19 pandemic has led to widespread changes in the way that people work, including an increase in remote work and changes in group dynamics. Social loafing, the phenomenon of reduced individual effort in group settings, has been widely studied in the literature. However, less is known about the potential impacts of social loafing on mental health and turnover intention in this relationship. In this study, we hypothesized that social loafing would be related to turnover intention and that mental health would mediate this relationship. To test these hypotheses, we conducted a cross-sectional survey of 700 full-time tourism employees in Egypt. The obtained data were analyzed by Partial least squares structural equation modeling (PLS-SEM). Our results indicated that social loafing was significantly related to turnover intention and negative mental health consequences significantly mediated this relationship. The results showed that stress (as a dimension of mental health) experienced by employees may act as a mediator between social loafing and turnover intention. On the other hand, depression and anxiety were not observed to have a similar mediating effect. This implies that stress could play a vital role in the decision-making process of employees who are contemplating leaving their job due to social loafing. These findings suggest that interventions aimed at reducing social loafing may have the added benefit of improving mental health and decreasing turnover intention in the workplace.
Synthesis and Characterisation of Fluorescent Novel Pt(II) Cyclometallated Complexes with Anticancer Activity
Authors: McGhie Brondwyn S. , Sakoff Jennette , Gilbert Jayne , Gordon Christopher P. , Aldrich-Wright Janice R.
Published: May 2023

Cancer poses a significant threat to global health and new treatments are required to improve the prognosis for patients. Previously, unconventional platinum complexes designed to incorporate polypyridyl ligands paired with diaminocyclohexane have demonstrated anticancer activity in KRAS mutated cells, previously thought to be undruggable and have cytotoxicity values up to 100 times better than cisplatin. In this work, these complexes were used as inspiration to design six novel cyclometallated examples, whose fluorescence could be exploited to better understand the mechanism of action of these kinds of platinum drugs. The cytotoxicity results revealed that these cyclometallated complexes (CMCs) have significantly different activity compared to the complexes that inspired them; they are as cytotoxic as cisplatin and have much higher selectivity indices in breast cancer cell lines (MCF10A/MCF-7). Complexes 1b, 2a, and 3b all had very high selectivity indexes compared to previous Pt(II) complexes. This prompted further investigation into their DNA binding properties, which revealed that they had good affinity to ctDNA, especially CMCs 1a and 3b. Their inherent fluorescence was successfully utilised in the calculation of their DNA binding affinity and could be useful in future work.
The β-1,3-Glucanase Degrades Callose at Plasmodesmata to Facilitate the Transport of the Ribonucleoprotein Complex in Pyrus betulaefolia
Authors: Yu Yunfei , Wang Shengyuan , Xu Chaoran , Xiang Ling , Huang Wenting , Zhang Xiao , Tian Baihui , Mao Chong , Li Tianzhong , Wang Shengnan
Published: May 2023

Grafting is widely used to improve the stress tolerance and the fruit yield of horticultural crops. Ribonucleoprotein complexes formed by mRNAs and proteins play critical roles in the communication between scions and stocks of grafted plants. In Pyrus betulaefolia, ankyrin was identified previously to promote the long-distance movement of the ribonucleoprotein complex(PbWoxT1-PbPTB3) by facilitating callose degradation at plasmodesmata. However, the mechanism of the ankyrin-mediated callose degradation remains elusive. In this study, we discovered a β-1,3-glucanase (EC 3.2.1.39, PbPDBG) using ankyrin as a bait from plasmodesmata by co-immunoprecipitation and mass spectrometry. Ankyrin was required for the plasmodesmata-localization of PbPDBG. The grafting and bombardment experiments indicated that overexpressing PbPDBG resulted in decreased callose content at plasmodesmata, and thereby promoting the long-distance transport of the ribonucleoprotein complex. Altogether, our findings revealed that PbPDBG was the key factor in ankyrin-mediated callose degradation at plasmodesmata.
Holoprosencephaly with a Special Form of Anophthalmia Result from Experimental Induction of bmp4, Oversaturating BMP Antagonists in Zebrafish
Authors: Bulk Johannes , Kyrychenko Valentyn , Rensinghoff Philipp M. , Ghaderi Ardekani Zahra , Heermann Stephan
Published: May 2023

Vision is likely our most prominent sense and a correct development of the eye is at its basis. Early eye development is tightly connected to the development of the forebrain. A single eye field and the prospective telencephalon are situated within the anterior neural plate (ANP). During normal development, both domains are split and consecutively, two optic vesicles and two telencephalic lobes emerge. If this process is hampered, the domains remain condensed at the midline. The resulting developmental disorder is termed holoprosencephaly (HPE). The typical ocular finding associated with intense forms of HPE is cyclopia. However, also anophthalmia and coloboma can be associated with HPE. Here, we report that a correct balance of Bone morphogenetic proteins (BMPs) and their antagonists are important for forebrain and eye field cleavage. Experimental induction of a BMP ligand results in a severe form of HPE showing anophthalmia. We identified a dysmorphic forebrain containing retinal progenitors, which we termed crypt-oculoid. Optic vesicle evagination is impaired due to a loss of rx3 and, consecutively, of cxcr4a. Our data further suggest that the subduction of prospective hypothalamic cells during neurulation and neural keel formation is affected by the induction of a BMP ligand.
Combined Transcriptome and Metabolome Analysis Reveals Adaptive Defense Responses to DON Induction in Potato
Authors: Zhao Biao , Yu Hang , Liu Dan , Wang Jiaqi , Feng Xu , He Fumeng , Qi Tianshuai , Du Chong , Wang Linlin , Wang Haifeng , Li Fenglan
Published: May 2023

Phytophthora infestans poses a serious threat to potato production, storage, and processing. Understanding plant immunity triggered by fungal elicitors is important for the effective control of plant diseases. However, the role of the potato stress response to Fusarium toxin deoxynivalenol (DON)-induced stress is still not fully understood. In this study, the metabolites of DON-treated potato tubers were studied for four time intervals using UPLC-MS/MS. We identified 676 metabolites, and differential accumulation metabolite analysis showed that alkaloids, phenolic acids, and flavonoids were the major differential metabolites that directly determined defense response. Transcriptome data showed that differentially expressed genes (DEGs) were significantly enriched in phenylpropane and flavonoid metabolic pathways. Weighted gene co-expression network analysis (WGCNA) identified many hub genes, some of which modulate plant immune responses. This study is important for understanding the metabolic changes, transcriptional regulation, and physiological responses of active and signaling substances during DON induction, and it will help to design defense strategies against Phytophthora infestans in potato.
Multiple Dosing and Preactivation of Mesenchymal Stromal Cells Enhance Efficacy in Established Pneumonia Induced by Antimicrobial-Resistant Klebsiella pneumoniae in Rodents
Authors: Byrnes Declan , Masterson Claire H. , Gonzales Hector E. , McCarthy Sean D. , O’Toole Daniel P. , Laffey John G.
Published: May 2023

Antimicrobial-resistant (AMR) bacteria, such as Klebsiella species, are an increasingly common cause of hospital-acquired pneumonia, resulting in high mortality and morbidity. Harnessing the host immune response to AMR bacterial infection using mesenchymal stem cells (MSCs) is a promising approach to bypass bacterial AMR mechanisms. The administration of single doses of naïve MSCs to ARDS clinical trial patient cohorts has been shown to be safe, although efficacy is unclear. The study tested whether repeated MSC dosing and/or preactivation, would attenuate AMR Klebsiella pneumonia-induced established pneumonia. Rat models of established K. pneumoniae-induced pneumonia were randomised to receive intravenous naïve or cytomix-preactivated umbilical cord MSCs as a single dose at 24 h post pneumonia induction with or without a subsequent dose at 48 h. Physiological indices, bronchoalveolar lavage (BAL), and tissues were obtained at 72 h post pneumonia induction. A single dose of naïve MSCs was largely ineffective, whereas two doses of MSCs were effective in attenuating Klebsiella pneumosepsis, improving lung compliance and oxygenation, while reducing bacteria and injury in the lung. Cytomix-preactivated MSCs were superior to naïve MSCs. BAL neutrophil counts and activation were reduced, and apoptosis increased. MSC therapy reduced cytotoxic BAL T cells, and increased CD4+/CD8+ ratios. Systemically, granulocytes, classical monocytes, and the CD4+/CD8+ ratio were reduced, and nonclassical monocytes were increased. Repeated doses of MSCs—particularly preactivated MSCs—enhance their therapeutic potential in a clinically relevant model of established AMR K. pneumoniae-induced pneumosepsis.
Sex Modulates Response to Renal-Tubule-Targeted Insulin Receptor Deletion in Mice
Authors: Sohail Soha , Akkawi Gabriella , Rechter Taylor , Fluitt Maurice B. , Ecelbarger Carolyn M.
Published: May 2023

Insulin facilitates renal sodium reabsorption and attenuates gluconeogenesis. Sex differences in this regulation have not been well characterized. Using tetracycline-inducible Cre-lox recombination, we knocked out (KO) the insulin receptor (InsR) from the renal tubule in adult male (M) and female (F) mice (C57Bl6 background) with a paired box 8 (PAX8) promoter. Body weights were not affected by the KO, but mean kidney weights were reduced in the KO mice (13 and 3%, in M and F, respectively, relative to wild-type (WT) mice). A microscopic analysis revealed 25 and 19% reductions in the proximal tubule (PT) and cortical collecting duct cell heights, respectively, in KOMs relative to WTMs. The reductions were 5 and 11% for KOFs. Western blotting of renal cortex homogenates showed decreased protein levels for the β and γ subunits of the epithelial sodium channel (ENaC) and the sodium-potassium-2-chloride cotransporter type 2 (NKCC2) in both sexes of KO mice; however, α-ENaC was upregulated in KOMs and downregulated in KOFs. Both sexes of KO mice cleared exogenously administered glucose faster than the WT mice and had lower semi-fasted, anesthetized blood glucose levels. However, KOMs (but not KOFs) demonstrated evidence of enhanced renal gluconeogenesis, including higher levels of renal glucose-6-phosphatase, the PT’s production of glucose, post-prandial blood glucose, and plasma insulin, whereas KOFs exhibited downregulation of renal high-capacity sodium glucose cotransporter (SGLT2) and upregulation of SGLT1; these changes appeared to be absent in the KOM. Overall, these findings suggest a sex-differential reliance on intact renal tubular InsR signaling which may be translationally important in type 2 diabetes, obesity, or insulin resistance when renal insulin signaling is reduced.
Impact of Gut Microbiota on the Peripheral Nervous System in Physiological, Regenerative and Pathological Conditions
Authors: Calabrò Sonia , Kankowski Svenja , Cescon Matilde , Gambarotta Giovanna , Raimondo Stefania , Haastert-Talini Kirsten , Ronchi Giulia
Published: May 2023

It has been widely demonstrated that the gut microbiota is responsible for essential functions in human health and that its perturbation is implicated in the development and progression of a growing list of diseases. The number of studies evaluating how the gut microbiota interacts with and influences other organs and systems in the body and vice versa is constantly increasing and several ‘gut–organ axes’ have already been defined. Recently, the view on the link between the gut microbiota (GM) and the peripheral nervous system (PNS) has become broader by exceeding the fact that the PNS can serve as a systemic carrier of GM-derived metabolites and products to other organs. The PNS as the communication network between the central nervous system and the periphery of the body and internal organs can rather be affected itself by GM perturbation. In this review, we summarize the current knowledge about the impact of gut microbiota on the PNS, with regard to its somatic and autonomic divisions, in physiological, regenerative and pathological conditions.
Emerging Therapies for the Treatment of Atherosclerotic Cardiovascular Disease: From Bench to Bedside
Authors: Kumric Marko , Urlic Hrvoje , Bozic Josko , Vilovic Marino , Ticinovic Kurir Tina , Glavas Duska , Miric Dino , Zanchi Jaksa , Bradaric-Slujo Anteo , Lozo Mislav , Borovac Josip A.
Published: May 2023

Primarily a consequence of sedentary lifestyle, atherosclerosis has already reached pandemic proportions, and with every year the burden of it is only increasing. As low-density lipoprotein cholesterol (LDL-C) represents a crucial factor in atherosclerosis formation and progression, stringent lipid-lowering therapy could conceivably be the key to preventing the unfavorable outcomes that arise as a consequence of atherosclerosis. The use of statins in lipid-lowering is often burdened by adverse events or is insufficient to prevent cardiovascular events as a monotherapy. Therefore, in the present review, the authors aimed to discuss the underlying mechanisms of dyslipidemia and associated atherosclerotic cardiovascular disease (ASCVD) and preclinical and clinical trials of novel therapeutic approaches to its treatment, some of which are still in the early stages of development. Apart from novel therapies, a novel change in perspective is needed. Specifically, the critical objective in the future management of ASCVD is to embrace emerging evidence in the field of atherosclerosis, because clinicians are often burden by common practice and personal experience, both of which have so far been shown to be futile in the setting of atherosclerosis.
CysB Is a Key Regulator of the Antifungal Activity of Burkholderia pyrrocinia JK-SH007
Authors: Yu Meng , Tang Yuwei , Lu Lanxiang , Kong Weiliang , Ye Jianren
Published: May 2023

Burkholderia pyrrocinia JK-SH007 can effectively control poplar canker caused by pathogenic fungi. Its antifungal mechanism remains to be explored. Here, we characterized the functional role of CysB in B. pyrrocinia JK-SH007. This protein was shown to be responsible for the synthesis of cysteine and the siderophore ornibactin, as well as the antifungal activity of B. pyrrocinia JK-SH007. We found that deletion of the cysB gene reduced the antifungal activity and production of the siderophore ornibactin in B. pyrrocinia JK-SH007. However, supplementation with cysteine largely restored these two abilities in the mutant. Further global transcriptome analysis demonstrated that the amino acid metabolic pathway was significantly affected and that some sRNAs were significantly upregulated and targeted the iron–sulfur metabolic pathway by TargetRNA2 prediction. Therefore, we suggest that, in B. pyrrocinia JK-SH007, CysB can regulate the expression of genes related to Fe–S clusters in the iron–sulfur metabolic pathway to affect the antifungal activity of B. pyrrocinia JK-SH007. These findings provide new insights into the various biological functions regulated by CysB in B. pyrrocinia JK-SH007 and the relationship between iron–sulfur metabolic pathways and fungal inhibitory substances. Additionally, they lay the foundation for further investigation of the main antagonistic substances of B. pyrrocinia JK-SH007.
Immunomodulatory Mechanism and Potential Application of Dental Pulp-Derived Stem Cells in Immune-Mediated Diseases
Authors: Min Qi , Yang Liqiong , Tian Hua , Tang Lu , Xiao Zhangang , Shen Jing
Published: May 2023

Dental pulp stem cells (DPSCs) are mesenchymal stem cells (MSCs) derived from dental pulp tissue, which have high self-renewal ability and multi-lineage differentiation potential. With the discovery of the immunoregulatory ability of stem cells, DPSCs have attracted much attention because they have similar or even better immunomodulatory effects than MSCs from other sources. DPSCs and their exosomes can exert an immunomodulatory ability by acting on target immune cells to regulate cytokines. DPSCs can also migrate to the lesion site to differentiate into target cells to repair the injured tissue, and play an important role in tissue regeneration. The aim of this review is to summarize the molecular mechanism and target cells of the immunomodulatory effects of DPSCs, and the latest advances in preclinical research in the treatment of various immune-mediated diseases, providing new reflections for their clinical application. DPSCs may be a promising source of stem cells for the treatment of immune-mediated diseases.
Gut Microbiome and Small RNA Integrative-Omic Perspective of Meconium and Milk-FED Infant Stool Samples
Authors: Kazakova Polina , Abasolo Nerea , de Cripan Sara Martinez , Marquès Emili , Cereto-Massagué Adrià , Garcia Lorena , Canela Núria , Tormo Ramón , Torrell Helena
Published: May 2023

The human gut microbiome plays an important role in health, and its initial development is conditioned by many factors, such as feeding. It has also been claimed that this colonization is guided by bacterial populations, the dynamic virome, and transkingdom interactions between host and microbial cells, partially mediated by epigenetic signaling. In this article, we characterized the bacteriome, virome, and smallRNome and their interaction in the meconium and stool samples from infants. Bacterial and viral DNA and RNA were extracted from the meconium and stool samples of 2- to 4-month-old milk-fed infants. The bacteriome, DNA and RNA virome, and smallRNome were assessed using 16S rRNA V4 sequencing, viral enrichment sequencing, and small RNA sequencing protocols, respectively. Data pathway analysis and integration were performed using the R package mixOmics. Our findings showed that the bacteriome differed among the three groups, while the virome and smallRNome presented significant differences, mainly between the meconium and stool of milk-fed infants. The gut environment is rapidly acquired after birth, and it is highly adaptable due to the interaction of environmental factors. Additionally, transkingdom interactions between viruses and bacteria can influence host and smallRNome profiles. However, virome characterization has several protocol limitations that must be considered.
An Integrative Approach to Investigate the Mode of Action of (−)-Dendroparishiol in Bacterial Meningitis: Computer-Aided Estimation of Biological Activity and Network Pharmacology
Authors: Limcharoen Thanchanok , Dasuni Wasana Peththa Wadu , Hasriadi  , Angsuwattana Pornpoom , Muangnoi Chawanphat , Warinhomhoun Sakan , Ongtanasup Tassanee , Sritularak Boonchoo , Vajragupta Opa , Rojsitthisak Pornchai , Towiwat Pasarapa
Published: May 2023

Bacterial meningitis remains one of the most prevalent infectious diseases worldwide. Although advances in medical care have improved mortality and morbidity, neurological complications remain high. Therefore, aside from antibiotics, therapeutic adjuvants targeting neuroinflammation are essential to combat the long-term neuronal sequelae of bacterial meningitis. In the present study, we propose (−)-dendroparishiol as a potential add-on therapy to improve neuroinflammation associated with bacterial meningitis. The biological activity of (−)-dendroparishiol was first predicted by computational analysis and further confirmed in vitro using a cell-based assay with LPS-induced BV-2 microglial cells. Biological pathways involved with (−)-dendroparishiol were identified by applying network pharmacology. Computational predictions of biological activity indicated possible attenuation of several inflammatory processes by (−)-dendroparishiol. In LPS-induced BV-2 microglial cells, (−)-dendroparishiol significantly reduced the expression of inflammatory mediators: iNOS, NO, COX-2, IL-6, and TNF-α. Molecular docking results demonstrated the potential iNOS and COX-2 inhibitory activity of (−)-dendroparishiol. Network pharmacological analysis indicated the plausible role of (−)-dendroparishiol in biological processes involved in oxidative stress and neuroinflammation with enrichment in neuroinflammatory pathways. Overall, this study provides scientific evidence for the potential application of (−)-dendroparishiol in the management of bacterial meningitis-associated neuroinflammation.
Intraocular Pressure-Lowering and Retina-Protective Effects of Exosome-Rich Conditioned Media from Human Amniotic Membrane Stem Cells in a Rat Model of Glaucoma
Authors: Seong Hye-Rim , Noh Chan Ho , Park Sangryong , Cho Sumin , Hong Seok-Jin , Lee Ah-young , Geum Dongho , Hong Soon-Cheol , Park Dongsun , Kim Tae Myoung , Choi Ehn-Kyoung , Kim Yun-Bae
Published: May 2023

Glaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important risk factor. Exosomes are lipid nanoparticles secreted from functional cells, including stem cells, and have been found to contain diverse functional molecules that control body function, inhibit inflammation, protect and regenerate cells, and restore damaged tissues. In the present study, exosome-rich conditioned media (ERCMs) were attained via hypoxic culture (2% O2) of human amniotic membrane mesenchymal stem cells (AMMSCs) and amniotic membrane epithelial stem cells (AMESCs) containing 50 times more exosome particles than normoxic culture (20% O2) medium (NCM). The exosome particles in ERCM were confirmed to be 77 nm in mean size and contain much greater amounts of growth factors (GFs) and neurotrophic factors (NFs) than those in NCM. The glaucoma-therapeutic effects of ERCMs were assessed in retinal cells and a hypertonic (1.8 M) saline-induced high-IOP animal model. CM-DiI-labeled AMMSC exosomes were found to readily penetrate the normal and H2O2-damaged retinal ganglion cells (RGCs), and AMMSC-ERCM not only facilitated retinal pigment epithelial cell (RPEC) proliferation but also protected against H2O2- and hypoxia-induced RPEC insults. The IOP of rats challenged with 1.8 M saline increased twice the normal IOP (12–17 mmHg) in a week. However, intravitreal injection of AMMSC-ERCM or AMESC-ERCM (3.9–4.5 × 108 exosomes in 10 μL/eye) markedly recovered the IOP to normal level in 2 weeks, similar to the effect achieved with platelet-derived growth factor-AB (PDGF-AB, 1.5 μg), a reference material. In addition, AMMSC-ERCM, AMESC-ERCM, and PDGF-AB significantly reversed the shrinkage of retinal layers, preserved RGCs, and prevented neural injury in the glaucoma eyes. It was confirmed that stem cell ERCMs containing large numbers of functional molecules such as GFs and NFs improved glaucoma by protecting retinal cells against oxidative and hypoxic injuries in vitro and by recovering IOP and retinal degeneration in vivo. Therefore, it is suggested that stem cell ERCMs could be a promising candidate for the therapy of glaucoma.
A Descriptive Whole-Genome Transcriptomics Study in a Stem Cell-Based Tool Predicts Multiple Tissue-Specific Beneficial Potential and Molecular Targets of Carnosic Acid
Authors: Ferdousi Farhana , Sasaki Kazunori , Fukumitsu Satoshi , Kuwata Hidetoshi , Nakajima Mitsutoshi , Isoda Hiroko
Published: May 2023

Carnosic acid (CA) is a phenolic diterpene widely distributed in herbal plants, rosemary and sage. Although its medicinal properties, such as antioxidant, antimicrobial, and neuroprotective effects, have been well-documented, its relevant biochemical processes and molecular targets have not been fully explored yet. In the present study, we conducted an untargeted whole-genome transcriptomics analysis to investigate CA-induced early biological and molecular events in human amniotic epithelial stem cells (hAESCs) with the aim of exploring its multiple tissue-specific functionalities and potential molecular targets. We found that seven days of CA treatment in hAESCs could induce mesoderm-lineage-specific differentiation. Tissue enrichment analysis revealed that CA significantly enriched lateral plate mesoderm-originated cardiovascular and adipose tissues. Further tissue-specific PPI analysis and kinase and transcription factor enrichment analyses identified potential upstream regulators and molecular targets of CA in a tissue-specific manner. Gene ontology enrichment analyses revealed the metabolic, antioxidant, and antifibrotic activities of CA. Altogether, our comprehensive whole-genome transcriptomics analyses offer a thorough understanding of the possible underlying molecular mechanism of CA.
Association of Mutations in Replicative DNA Polymerase Genes with Human Disease: Possible Application of Drosophila Models for Studies
Authors: Yamaguchi Masamitsu , Cotterill Sue
Published: May 2023

Replicative DNA polymerases, such as DNA polymerase α-primase, δ and ε, are multi-subunit complexes that are responsible for the bulk of nuclear DNA replication during the S phase. Over the last decade, extensive genome-wide association studies and expression profiling studies of the replicative DNA polymerase genes in human patients have revealed a link between the replicative DNA polymerase genes and various human diseases and disorders including cancer, intellectual disability, microcephalic primordial dwarfism and immunodeficiency. These studies suggest the importance of dissecting the mechanisms involved in the functioning of replicative DNA polymerases in understanding and treating a range of human diseases. Previous studies in Drosophila have established this organism as a useful model to understand a variety of human diseases. Here, we review the studies on Drosophila that explored the link between DNA polymerases and human disease. First, we summarize the recent studies linking replicative DNA polymerases to various human diseases and disorders. We then review studies on replicative DNA polymerases in Drosophila. Finally, we suggest the possible use of Drosophila models to study human diseases and disorders associated with replicative DNA polymerases.
Maize Transcription Factor ZmHsf28 Positively Regulates Plant Drought Tolerance
Authors: Liu Lijun , Zhang Yuhan , Tang Chen , Shen Qinqin , Fu Jingye , Wang Qiang
Published: May 2023

Identification of central genes governing plant drought tolerance is fundamental to molecular breeding and crop improvement. Here, maize transcription factor ZmHsf28 is identified as a positive regulator of plant drought responses. ZmHsf28 exhibited inducible gene expression in response to drought and other abiotic stresses. Overexpression of ZmHsf28 diminished drought effects in Arabidopsis and maize. Gene silencing of ZmHsf28 via the technology of virus-induced gene silencing (VIGS) impaired maize drought tolerance. Overexpression of ZmHsf28 increased jasmonate (JA) and abscisic acid (ABA) production in transgenic maize and Arabidopsis by more than two times compared to wild-type plants under drought conditions, while it decreased reactive oxygen species (ROS) accumulation and elevated stomatal sensitivity significantly. Transcriptomic analysis revealed extensive gene regulation by ZmHsf28 with upregulation of JA and ABA biosynthesis genes, ROS scavenging genes, and other drought related genes. ABA treatment promoted ZmHsf28 regulation of downstream target genes. Specifically, electrophoretic mobility shift assays (EMSA) and yeast one-hybrid (Y1H) assay indicated that ZmHsf28 directly bound to the target gene promoters to regulate their gene expression. Taken together, our work provided new and solid evidence that ZmHsf28 improves drought tolerance both in the monocot maize and the dicot Arabidopsis through the implication of JA and ABA signaling and other signaling pathways, shedding light on molecular breeding for drought tolerance in maize and other crops.
Multiplex Lithographic SERS Aptasensor for Detection of Several Respiratory Viruses in One Pot
Authors: Kukushkin Vladimir , Ambartsumyan Oganes , Subekin Alexei , Astrakhantseva Anna , Gushchin Vladimir , Nikonova Alexandra , Dorofeeva Anastasia , Zverev Vitaly , Keshek Anna , Meshcheryakova Nadezda , Zaborova Olga , Gambaryan Alexandra , Zavyalova Elena
Published: May 2023

Rapid and reliable techniques for virus identification are required in light of recurring epidemics and pandemics throughout the world. Several techniques have been distributed for testing the flow of patients. Polymerase chain reaction with reverse transcription is a reliable and sensitive, though not rapid, tool. The antibody-based strip is a rapid, though not reliable, and sensitive tool. A set of alternative tools is being developed to meet all the needs of the customer. Surface-enhanced Raman spectroscopy (SERS) provides the possibility of single molecule detection taking several minutes. Here, a multiplex lithographic SERS aptasensor was developed aiming at the detection of several respiratory viruses in one pot within 17 min. The four labeled aptamers were anchored onto the metal surface of four SERS zones; the caught viruses affect the SERS signals of the labels, providing changes in the analytical signals. The sensor was able to decode mixes of SARS-CoV-2 (severe acute respiratory syndrome coronavirus two), influenza A virus, respiratory syncytial virus, and adenovirus within a single experiment through a one-stage recognition process.