bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytotoxic potential on human breast and lung cancer cells of the biosynthesized gold nanoparticles from the reduction of chloroauric acid by lactic acid isolated from Lactobacillus acidophilus
Authors: Repotente Elmer Casley , Carreon Angelo Jose , Devanadera Mark Kevin , Esmalla Maria Salvacion , Santiago-Bautista Myla
Published: October 2022

Chemotherapy side effects, drug resistance, and tumor metastasis hinder the progress of cancer treatments, which has led to cancer patients having a poor prognosis. In recent years, nanoparticles (NPs) have become an emerging trend in drug delivery technology. The biosynthesis of gold nanoparticles (AuNPs) from lactic acid as probiotic metabolites is a cost-efficient and eco-friendly approach due to the widespread availability and ease of culturing methods. Here, AuNPs were synthesized by reducing chloroauric acid using lactic acid isolated from the probiotic Lactobacillus acidophilus. Surface characterization of the biosynthesized gold nanoparticles was performed by UV-visible spectroscopy, field emission scanning electron microscopy with energy dispersive spectroscopy (FESEM-EDS), and atomic force microscopy (AFM). The distinct peak of the AuNPs in the UV-Vis spectra at around 520 nm indicates the nanoscale level of the gold particles. SEM images of the shape of the biosynthesized AuNPs were found to be small, smooth spherical particles with sizes ranging from 6 to 12 nm. AFM results agree with SEM images, showing AuNPs with sizes ranging from 4 to 15 nm. The anticancer activities of the biosynthesized AuNPs have been investigated by cytotoxicity (MTT) and apoptosis (Caspase 3/7) assay in the human breast and lung cancer cells (MCF7 and A549), and control (myoblasts). MTT assay showed AuNPs’ cytotoxic potential on cancer cells (MCF7 and A549) compared to normal cells (myoblasts). Cytotoxicity and apoptosis assay of the synthesized AuNPs exhibit toxicity against human breast adenocarcinoma cells (MCF7, IC50 of 0.075 mM) and human lung cancer cells (A549, IC50 of 0.07 mM), as shown evidently in the cellular morphology and in the DNA-stained nucleus. Only MCF7 cells exhibited apoptotic events upon AuNP treatment. AuNPs proved to be safe as they are non-toxic against normal cells and myoblasts. Interestingly, the biosynthesized AuNPs were absorbed by the cells and are present in the cytosol, thus demonstrating selectivity toward breast and lung cancer cells used. The study showed the first evidence that AuNPs can be synthesized using lactic acid as a reducing agent and capping agent isolated from the probiotic Lactobacillus acidophilus. The results suggested potential cancer chemotherapeutic leads and targeted delivery in human breast and lung cancers.
Prognostic value of acute cor pulmonale in COVID-19-related pneumonia: A prospective study
Authors: Beyls Christophe , Martin Nicolas , Booz Thomas , Viart Christophe , Boisgard Solenne , Daumin Camille , Crombet Maxime , Epailly Julien , Huette Pierre , Dupont Hervé , Abou-Arab Osama , Mahjoub Yazine
Published: October 2022

Background

It is known that acute cor pulmonale (ACP) worsens the prognosis of non-coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (NC-ARDS). The ACP risk score evaluates the risk of ACP occurrence in mechanically ventilated patients with NC-ARDS. There is less data on the risk factors and prognosis of ACP induced by COVID-19-related pneumonia.

Objective

The objective of this study was to evaluate the prognostic value of ACP, assessed by transthoracic echocardiography (TTE) and clinical factors associated with ACP in a cohort of patients with COVID-19-related pneumonia.

Materials and methods

Between February 2020 and June 2021, patients admitted to intensive care unit (ICU) at Amiens University Hospital for COVID-19-related pneumonia were assessed by TTE within 48 h of admission. ACP was defined as a right ventricle/left ventricle area ratio of >0.6 associated with septal dyskinesia. The primary outcome was mortality at 30 days.

Results

Among 146 patients included, 36% (n = 52/156) developed ACP of which 38% (n = 20/52) were non-intubated patients. The classical risk factors of ACP (found in NC-ARDS) such as PaCO2 >48 mmHg, driving pressure >18 mmHg, and PaO2/FiO2 < 150 mmHg were not associated with ACP (all P-values > 0.1). The primary outcome occurred in 32 (22%) patients. More patients died in the ACP group (n = 20/52 (38%) vs. n = 12/94 (13%), P = 0.001). ACP [hazards ratio (HR) = 3.35, 95%CI [1.56–7.18], P = 0.002] and age >65 years (HR = 2.92, 95%CI [1.50–5.66], P = 0.002) were independent risk factors of 30-day mortality.

Conclusion

ACP was a frequent complication in ICU patients admitted for COVID-19-related pneumonia. The 30-day-mortality was 38% in these patients. In COVID-19-related pneumonia, the classical risk factors of ACP did not seem relevant. These results need confirmation in further studies.
Postoperative analgesia efficacy of erector spinae plane block in adult abdominal surgery: A systematic review and meta-analysis of randomized trials
Authors: Gao Yuzheng , Liu Lidan , Cui Yuning , Zhang Jiaxin , Wu Xiuying
Published: October 2022

Objectives

Erector spinae plane block (ESPB) has been used for many thoracic and abdominal surgeries. However, evidence of its analgesic efficacy following abdominal surgery, compared with that of thoracic analgesia, is insufficient. Our study explored the analgesic effect of ESPB after abdominal surgery.

Methods

We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Primary outcomes were pain scores at 6, 12 and 24 h and 24-h opioid consumption. Secondary outcomes included time to first rescue analgesia, length of hospital stay, and incidence of postoperative nausea and vomiting (PONV). We calculated standardized mean differences (SMDs) with 95% confidence intervals (CIs) for primary outcomes and mean differences (MDs) and risk ratios (RRs) with 95% CIs for secondary outcomes.

Results

We systematically included 1,502 cases in 24 trials. Compared with placebo, ESPB significantly reduced pain scores at 6 h (SMD −1.25; 95% CI −1.79 to −0.71), 12 h (SMD −0.85; 95% CI −1.33 to −0.37) and 24 h (SMD −0.84; 95% CI −1.30 to −0.37) and 24-h opioid consumption (SMD −0.62; 95% CI −1.19 to −0.06) post-surgery. ESPB prolonged the time to first rescue analgesia and decreased the incidence of PONV. Compared with transversus abdominal plane block (TAPB), ESPB significantly reduced pain scores at 6, 12, and 24 h and 24-h opioid consumption and prolonged the time to first rescue analgesia postsurgically. Furthermore, subgroup analysis showed that ESPB significantly reduced pain scores at various time points and opioid consumption within 24 h after laparoscopic cholecystectomy, percutaneous nephrolithotomy and bariatric surgery.

Conclusion

Compared with placebo, ESPB improves the postoperative analgesic efficacy after abdominal surgery. Furthermore, our meta-analysis confirmed that ESPB provides more beneficial analgesic efficacy than TAPB.

Systematic review registration

[https://www.crd.york.ac.uk/PROSPEROFILES/301491_STRATEGY_20220104.pdf], identifier [CRD42022301491].
Comparison between 10 and 12 mg doses of intrathecal hyperbaric (0.5%) bupivacaine on sensory block level after first spinal failure in cesarean section: A double-blind, randomized clinical trial
Authors: Manouchehrian Nahid , Rahimi-Bashar Farshid , Pirdehghan Azar , Shahmoradi Fatemeh
Published: October 2022

Background

Reducing adverse effects during cesarean delivery and improving the quality of sensory blocks with appropriate doses of intrathecal hyperbaric bupivacaine can play an important role in the safe management of cesarean delivery. The aim of this study was to compare the doses of 10 and 12 mg of intrathecal hyperbaric bupivacaine 0.5% on sensory block level after first spinal failure in cesarean section (CS).

Methods

In this double-blind, randomized clinical trial, 40 candidates of CS after first spinal failure with class I-II based on American Society of Anesthesiologists (ASA) were randomly assigned into two equal groups (n = 20). Group A and B received the spinal anesthesia with 10 mg and 12 mg of hyperbaric bupivacaine (0.5%), respectively. Maximum levels of sensory block, motor block quality, and vital signs were measured in two groups by 60 min after SPA. Incidence of SPA complications during surgery were also recorded. Data were analyzed by SPSS ver.21 software using repeated measures analysis of variance at 95% confidence interval (CI) level.

Results

Excellent quality of sensory blocks and complete quality of motor blocks were achieved in all participants (100%). However, the mean time to onset of anesthesia (4.47 ± 0.69 vs. 3.38 ± 0.47, P < 0.001) and time to reach T10 level (60.73 ± 11.92 vs. 79.00 ± 19.21, P < 0.001) in the Group A, were significantly shorter than in the patients of Group B. The incidence of hypotension (P = 0.001), nausea/vomiting (P = 0.007) and bradycardia (P = 0.012) as well as administration of ephedrine and atropine were significantly higher in Group B compared to Group A.

Conclusion

Spinal anesthesia can be safely repeated with a 10 mg of hyperbaric bupivacaine 0.5% in a caesarean section after the initial spinal failure.

Clinical trial registration

[https://en.irct.ir/trial/40714], identifier [IRCT20120915010841N20].
Analysis of the epidemiological burden of acne vulgaris in China based on the data of global burden of disease 2019
Authors: Wang Yan , Xiao ShengXiang , Ren JianWen , Zhang YanFei
Published: October 2022

Acne vulgaris is a chronic, inflammatory skin disease, which has brought an increasing disease burden to patients and society. But there is no systematic study on the disease burden and social development of acne vulgaris in China. This study aimed to analyze the epidemiological burden and trend of acne vulgaris in China from 1990 to 2019 based on the data in the global burden of disease 2019 (GBD 2019). The number of incidences/illnesses, age-standardized incidence/prevalence rates, disability-adjusted life years (DALYs), and DALY rate of acne vulgaris in China from 1990 to 2019 were obtained from the GBD 2019 to evaluate the epidemiological trends and age-period-cohort trends. The associations between disease burden and social development degrees were analyzed using a sociodemographic index. In 2019, the age-standardized prevalence and incidence of acne vulgaris in China were both at low levels in the world. From 1990 to 2019, the prevalent cases and incident cases of acne vulgaris in China rose firstly and then fell (peaked in 2005 and 2003, respectively), and the age-standardized prevalence/incidence/DALY rates showed growth trends continuously. The prevalence of acne vulgaris peaked in the 15–19 age group while the incidence peak age was 10–14 years old and there was an obvious gender difference, females were higher than males. With the increase of sociodemographic index (SDI) value, the morbidity of acne vulgaris showed a linear growth trend (P < 0.05). From 1990 to 2019, the disease burden of acne vulgaris is increasing in China, which is correlated with social and medical development. Active research on the epidemiological data of acne vulgaris and its relationship with the level of social development is important for both the diagnosis and treatment of acne vulgaris and for the development of health policies.
Bone marrow stromal cell antigen-1 (CD157) regulated by sphingosine kinase 2 mediates kidney fibrosis
Authors: Inoue Tsuyoshi , Nakamura Yasuna , Tanaka Shinji , Kohro Takahide , Li Lisa X. , Huang Liping , Yao Junlan , Kawamura Suzuka , Inoue Reiko , Nishi Hiroshi , Fukaya Daichi , Uni Rie , Hasegawa Sho , Inagi Reiko , Umene Ryusuke , Wu Chia-Hsien , Ye Hong , Bajwa Amandeep , Rosin Diane L. , Ishihara Katsuhiko , Nangaku Masaomi , Wada Youichiro , Okusa Mark D.
Published: October 2022

Chronic kidney disease is a progressive disease that may lead to end-stage renal disease. Interstitial fibrosis develops as the disease progresses. Therapies that focus on fibrosis to delay or reverse progressive renal failure are limited. We and others showed that sphingosine kinase 2-deficient mice (Sphk2–/–) develop less fibrosis in mouse models of kidney fibrosis. Sphingosine kinase2 (SphK2), one of two sphingosine kinases that produce sphingosine 1-phosphate (S1P), is primarily located in the nucleus. S1P produced by SphK2 inhibits histone deacetylase (HDAC) and changes histone acetylation status, which can lead to altered target gene expression. We hypothesized that Sphk2 epigenetically regulates downstream genes to induce fibrosis, and we performed a comprehensive analysis using the combination of RNA-seq and ChIP-seq. Bst1/CD157 was identified as a gene that is regulated by SphK2 through a change in histone acetylation level, andBst1–/–mice were found to develop less renal fibrosis after unilateral ischemia-reperfusion injury, a mouse model of kidney fibrosis. Although Bst1 is a cell-surface molecule that has a wide variety of functions through its varied enzymatic activities and downstream intracellular signaling pathways, no studies on the role of Bst1 in kidney diseases have been reported previously. In the current study, we demonstrated that Bst1 is a gene that is regulated by SphK2 through epigenetic change and is critical in kidney fibrosis.
Finding the best combination of autochthonous microorganisms with the most effective biosorption ability for heavy metals removal from wastewater
Authors: Jakovljević Violeta , Grujić Sandra , Simić Zoran , Ostojić Aleksandar , Radojević Ivana
Published: October 2022

The presence of heavy metals (HMs) in the environment represents a serious environmental problem. In this regard, this work was conceived with the aim of finding, among indigenous microorganisms, the species and their combinations with the best biosorption activity for the following HMs: zinc, lead, cadmium, copper, and nickel. The experiment was carried out in several steps: (1) isolation and identification of microbial strains from the Central Effluent Treatment Plant’s wastewater; (2) studying the interaction of microorganisms and the ability to form biofilms in 96-well plates; (3) testing the resistance of biofilms to HMs; (4) testing the growth of biofilms on AMB media carriers in the presence of HMS; and (5) biosorption assay. The selected strains used in this study were: Enterobacter cloacae, Klebsiella oxytoca, Serratia odorifera, and Saccharomyces cerevisiae. The best biofilm producers in control medium were K. oxytoca/S. odorifera (KS), followed by K. oxytoca/S. odorifera/S. cerevisiae (KSC), and E. cloacae/K. oxytoca/S. odorifera (EKS) after 10 days of incubation. Mixed cultures composed of three species showed the highest resistance to the presence of all tested metals. The best biosorption capacity was shown by KSC for Cu2+ (99.18%), followed by EKS for Pb2+ (99.14%) and Cd2+ (99.03%), K. oxytoca for Ni2+ (98.47%), and E. cloacae for Zn2+ (98.06%). This research offers a novel approach to using mixed biofilms for heavy metal removal processes as well as its potential application in the bioremediation of wastewater.
Biochar-mediated changes in the microbial communities of rhizosphere soil alter the architecture of maize roots
Authors: Yan Han , Cong Mengfei , Hu Yang , Qiu Chunchen , Yang Zailei , Tang Guangmu , Xu Wanli , Zhu Xinping , Sun Xia , Jia Hongtao
Published: October 2022

Aeolian sandy soil is a key resource for supporting food production on a global scale; however, the growth of crops in Aeolian sandy soil is often impaired due to its poor physical properties and lack of nutrients and organic matter. Biochar can be used to enhance the properties of Aeolian sandy soil and create an environment more suitable for crop growth, but the long-term effects of biochar on Aeolian sandy soil and microbial communities need to be clarified. Here, a field experiment was conducted in which biochar was applied to a maize (Zea mays L.) field in a single application at different rates: CK, 0 Mg ha−1; C1, 15.75 Mg ha−1; C2, 31.50 Mg ha−1; C3, 63.00 Mg ha−1; and C4, 126.00 Mg ha−1. After 7 years of continuous maize cropping, verify the relationship between root architecture and soil microbial communities under biochar application using a root scanner and 16S/ITS rRNA gene sequencing. The application of biochar promoted the growth of maize. Specifically, total root length, total root surface area, total root volume, and root biomass were 13.99–17.85, 2.52–4.69, 23.61–44.41, and 50.61–77.80% higher in treatments in which biochar was applied (C2, C3, and C4 treatments) compared with the control treatment, respectively. Biochar application increased the diversity of bacterial communities, the ACE index, and Chao 1 index of C1, C2, C3, and C4 treatments increased by 5.83–8.96 and 5.52–8.53%, respectively, compared with the control treatment, and significantly changed the structure of the of bacterial communities in rhizosphere soil. However, there was no significant change in the fungal community. The growth of maize roots was more influenced by rhizosphere bacteria and less by fungal community. A microbial co-occurrence network revealed strong associations among rhizosphere microorganisms. The core taxa (Module hubs taxa) of the bulk soil microbial co-occurrence network were closely related to the total length and total surface area of maize roots, and the core taxa (Connectors taxa) of the rhizosphere soil were closely related to total root length. Overall, our findings indicate that the application of biochar promotes the growth of maize roots in aeolian sandy soil through its effects on bacterial communities in rhizosphere soil.
Advances in artificial intelligence-based microbiome for PMI estimation
Authors: Wang Ziwei , Zhang Fuyuan , Wang Linlin , Yuan Huiya , Guan Dawei , Zhao Rui
Published: October 2022

Postmortem interval (PMI) estimation has always been a major challenge in forensic science. Conventional methods for predicting PMI are based on postmortem phenomena, metabolite or biochemical changes, and insect succession. Because postmortem microbial succession follows a certain temporal regularity, the microbiome has been shown to be a potentially effective tool for PMI estimation in the last decade. Recently, artificial intelligence (AI) technologies shed new lights on forensic medicine through analyzing big data, establishing prediction models, assisting in decision-making, etc. With the application of next-generation sequencing (NGS) and AI techniques, it is possible for forensic practitioners to improve the dataset of microbial communities and obtain detailed information on the inventory of specific ecosystems, quantifications of community diversity, descriptions of their ecological function, and even their application in legal medicine. This review describes the postmortem succession of the microbiome in cadavers and their surroundings, and summarizes the application, advantages, problems, and future strategies of AI-based microbiome analysis for PMI estimation.
Phase-variable Type I methyltransferase M.NgoAV from Neisseria gonorrhoeae FA1090 regulates phasevarion expression and gonococcal phenotype
Authors: Adamczyk-Poplawska Monika , Bacal Pawel , Mrozek Agnieszka , Matczynska Natalia , Piekarowicz Andrzej , Kwiatek Agnieszka
Published: October 2022

The restriction-modification (RM) systems are compared to a primitive, innate, prokaryotic immune system, controlling the invasion by foreign DNA, composed of methyltransferase (MTase) and restriction endonuclease. The biological significance of RM systems extends beyond their defensive function, but the data on the regulatory role of Type I MTases are limited. We have previously characterized molecularly a non-canonical Type I RM system, NgoAV, with phase-variable specificity, encoded by Neisseria gonorrhoeae FA1090. In the current work, we have investigated the impact of methyltransferase NgoAV (M.NgoAV) activity on gonococcal phenotype and on epigenetic control of gene expression. For this purpose, we have constructed and studied genetic variants (concerning activity and specificity) within M.NgoAV locus. Deletion of M.NgoAV or switch of its specificity had an impact on phenotype of N. gonorrhoeae. Biofilm formation and planktonic growth, the resistance to antibiotics, which target bacterial peptidoglycan or other antimicrobials, and invasion of human epithelial host cells were affected. The expression of genes was deregulated in gonococcal cells with knockout M.NgoAV gene and the variant with new specificity. For the first time, the existence of a phasevarion (phase-variable regulon), directed by phase-variable Type I MTase, is demonstrated.
Host-encoded, cell surface-associated exopolysaccharide required for adsorption and infection by lactococcal P335 phage subtypes
Authors: Millen Anne M. , Romero Dennis A. , Horvath Philippe , Magill Damian , Simdon Laura
Published: October 2022

Lactococcus lactis and Lactococcus cremoris compose commercial starter cultures widely used for industrial dairy fermentations. Some lactococcal strains may produce exopolysaccharides (EPS), which have technological applications, including texture production and phage resistance. Two distinct gene clusters associated with EPS production, designated 6073-like and 7127-like, were identified on plasmids in lactococcal strains. Infectivity of two subsets of P335 group phages, distinguished based on their single-component baseplate/receptor-binding protein nucleotide sequences, was correlated to the presence of a host-encoded 6073-like or 7127-like eps gene cluster. Furthermore, phages belonging to these subsets differentially adsorbed to lactococcal strains harboring the respective eps gene cluster. Loss of the respective EPS-encoding plasmid from a fully phage-sensitive strain resulted in loss of phage adsorption and resistance to the phage. Transmission electron microscopy (TEM) showed that the EPS produced by strains encoding the 6073-like or 7127-like eps gene clusters are cell-surface associated, which, coupled with phage plaquing and adsorption data, shows that specific capsular EPS are involved in host recognition by certain P335 phage subgroups. To our knowledge, this is the first description of the involvement of EPS produced via the Wzx/Wzy-dependent pathway in phage sensitivity of L. lactis or L. cremoris. This study also shows strains that do not appear to be phage-related based on plaque formation may still be related by phage adsorption and indicates that optimal formulation of phage-robust cultures should take into account the EPS type of individual strains.
Ferroptosis regulator SLC7A11 is a prognostic marker and correlated with PD-L1 and immune cell infiltration in liver hepatocellular carcinoma
Authors: Liang Yimin , Su Shijie , Lun Zhaoxia , Zhong Zishao , Yu Weifeng , He Guihua , Wang Qi , Wang Jing , Huang Suiping
Published: October 2022

Background: Liver hepatocellular carcinoma (LIHC) is a complicated disease with poor survival and lack of viable treatment options. The roles of ferroptosis and immunotherapy in LIHC are increasingly prominent, but the interplay of ferroptosis with the tumor microenvironment (TME) in LIHC is currently under-investigated.

Methods: In this study, we analyzed normal liver tissues and tumor tissues from the TCGA and GTEx databases to obtain differentially expressed ferroptosis-related genes (FRGs). We then clustered LIHC based on the expression levels of selected FRGs and acquired distinct subtypes with significant heterogeneity regarding survival prognoses, PD-L1 expression, and immune cell infiltration. The correlation of those FRGs with TME in LIHC and pan-cancer analysis was also investigated. GO functional annotations and KEGG pathway analyses were performed to investigate the potential reactions of the obtained differentially expressed genes (DEGs). Further external validation was performed using microarrays on the GEO database and the key ferroptosis regulator SLC7A11 expression between LIHC and normal cells was detected by Western blotting.

Results: A large proportion of genes were upregulated in the LIHC group. Among three clusters, cluster 3 had the worst prognosis combined with the highest PD-L1 expression and was positively correlated with various immune cells. Subsequently, survival analysis and Cox regression analysis screened out SLC7A11 as an independent prognostic factor in LIHC featured strong PD-L1 expression and unfavorable survival time. We filter out SLC7A11 as an independent prognostic signature in LIHC patients with strongly associated PD-L1 expression and unfavorable survival probability. In the pan-cancer analysis, high expression of SLC7A11 showed poor overall survival in seven cancers, while the correlation between immune checkpoints (ICs) and SLC7A11 varied by cancer type, indicating the potential therapeutic effects of SLC7A11 in cancers other than LIHC. Western blot was further employed to verify the expression of SLC7A11 in LIHC in vitro.

Conclusion: Ferroptosis and TME synergistically play key roles in oncogenesis and progression of LIHC, and SLC7A11 can be used as a predictive biomarker for customized immunotherapy.
Inhibition of phosphodiesterase: A novel therapeutic target for the treatment of mild cognitive impairment and Alzheimer’s disease
Authors: Sheng Jianwen , Zhang Shanjin , Wu Lule , Kumar Gajendra , Liao Yuanhang , GK Pratap , Fan Huizhen
Published: October 2022

Alzheimer’s disease (AD) is the most common form of dementia and is ranked as the 6th leading cause of death in the US. The prevalence of AD and dementia is steadily increasing and expected cases in USA is 14.8 million by 2050. Neuroinflammation and gradual neurodegeneration occurs in Alzheimer’s disease. However, existing medications has limitation to completely abolish, delay, or prevent disease progression. Phosphodiesterases (PDEs) are large family of enzymes to hydrolyze the 3’-phosphodiester links in cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in signal-transduction pathways for generation of 5’-cyclic nucleotides. It plays vital role to orchestrate several pharmacological activities for proper cell functioning and regulating the levels of cAMP and cGMP. Several evidence has suggested that abnormal cAMP signaling is linked to cognitive problems in neurodegenerative disorders like AD. Therefore, the PDE family has become a widely accepted and multipotential therapeutic target for neurodegenerative diseases. Notably, modulation of cAMP/cGMP by phytonutrients has a huge potential for the management of AD. Natural compounds have been known to inhibit phosphodiesterase by targeting key enzymes of cGMP synthesis pathway, however, the mechanism of action and their therapeutic efficacy has not been explored extensively. Currently, few PDE inhibitors such as Vinpocetine and Nicergoline have been used for treatment of central nervous system (CNS) disorders. Considering the role of flavonoids to inhibit PDE, this review discussed the therapeutic potential of natural compounds with PDE inhibitory activity for the treatment of AD and related dementia.
Verbal intelligence and leisure activities are associated with cognitive performance and resting-state electroencephalogram
Authors: Ferrari-Díaz Martina , Bravo-Chávez Ricardo Iván , Silva-Pereyra Juan , Fernández Thalía , García-Peña Carmen , Rodríguez-Camacho Mario
Published: October 2022

Cognitive reserve (CR) is the adaptability of cognitive processes that helps to explain differences in the susceptibility of cognitive or daily functions to resist the onslaught of brain-related injury or the normal aging process. The underlying brain mechanisms of CR studied through electroencephalogram (EEG) are scarcely reported. To our knowledge, few studies have considered a combination of exclusively dynamic proxy measures of CR. We evaluated the association of CR with cognition and resting-state EEG in older adults using three of the most frequently used dynamic proxy measures of CR: verbal intelligence, leisure activities, and physical activities. Multiple linear regression analyses with the CR proxies as independent variables and cognitive performance and the absolute power (AP) on six resting-state EEG components (beta, alpha1, alpha2, gamma, theta, and delta) as outcomes were performed. Eighty-eight healthy older adults aged 60–77 (58 female) were selected from previous study data. Verbal intelligence was a significant positive predictor of perceptual organization, working memory, processing speed, executive functions, and central delta power. Leisure activities were a significant positive predictor of posterior alpha2 power. The dynamic proxy variables of CR are differently associated with cognitive performance and resting-state EEG. Implementing leisure activities and tasks to increase vocabulary may promote better cognitive performance through compensation or neural efficiency mechanisms.
RETRACTED: Characteristics of cognitive function in patients with cerebellar infarction and its association with lesion location
Authors: Liu Qi , Liu Chang , Zhang Yumei
Published: October 2022

Objective: This study aimed to explore the characteristics of cognitive function in patients with cerebellar infarction and its association with lesion location.

Methods: Forty-five patients with isolated cerebellar infarction were collected in the Department of Neurology, Beijing Tiantan Hospital. Thirty healthy controls were recruited matched by age and education. Global cognitive function was evaluated by using Addenbrooke’s Cognitive Examination version III (ACE-III). An extensive neuropsychological assessment battery was also tested to evaluate the characteristics of each cognitive domain. 3D slicer software was used to draw the lesion, and evaluate the lesions’ volume, side, and location. Group analysis was used to compare the differences in cognitive performance between patients and healthy controls, and patients with left and right cerebellar hemisphere infarction. Spearman analysis was used to explore the correlation between cognitive function and lesion volume. We also subdivided each patient’s lesions according to the cerebellar atlas to identify the specific cerebellar location related to cognitive decline.

Results: Patients with cerebellar infarction had a lower ACE-III score compared with the healthy group (87.9 ± 6.2 vs. 93.7 ± 2.9, p < 0.001), and 22 (48.9%) patients were diagnosed with cognitive impairment. The z-transformed score of attention and executive function in the patients’ group was −0.9 ± 1.4 and −0.8 ± 1.0 respectively, with 19 (43.2%) and 23 (56.4%) patients impaired. Compared with healthy controls, the relative risk ratio with 95% confidence interval (CI) for impairment in attention and executive function were 3.24 (1.22–8.57) and 3.39 (1.45–7.89). However, only 10 (22.1%) patients showed impairment in more than two cognitive domains. Compared with the left lesion group, patients with right cerebellar infarction showed significantly impaired executive function (−1.1 ± 0.3 vs. −0.5 ± 0.2, p = 0.01). And the cerebellar posterior lobe regions, especially lobules VI, VIII, and IX, were explored to have lower cognitive performance. Furthermore, lesion volume was identified to be associated with the ACE-III score (r = −0.37, p = 0.04).

Conclusion: We identified that cerebellar involvement in cognition, especially in attention processing and executive function. Cerebellar right-sided lateralization of cognition and functional topography were also revealed in the current study.
Associations between blood-based biomarkers of Alzheimer’s disease with cognition in motoric cognitive risk syndrome: A pilot study using plasma Aβ42 and total tau
Authors: Chen Pei-Hao , Lin Sang-I , Liao Ying-Yi , Hsu Wei-Ling , Cheng Fang-Yu
Published: October 2022

Background

Motoric cognitive risk (MCR) syndrome is a conceptual construct that combines slow gait speed with subjective cognitive complaints and has been shown to be associated with an increased risk of developing dementia. However, the relationships between the pathology of Alzheimer’s disease (AD) and MCR syndrome remain uncertain. Therefore, the purpose of this study was to determine the levels of plasma AD biomarkers (Aβ42 and total tau) and their relationships with cognition in individuals with MCR.

Materials and methods

This was a cross-sectional pilot study that enrolled 25 individuals with normal cognition (NC), 27 with MCR, and 16 with AD. Plasma Aβ42 and total tau (t-tau) levels were measured using immunomagnetic reduction (IMR) assays. A comprehensive neuropsychological assessment was also performed.

Results

The levels of plasma t-tau proteins did not differ significantly between the MCR and AD groups, but that of plasma t-tau was significantly increased in the MCR and AD groups, compared to the NC group. Visuospatial performance was significantly lower in the MCR group than in the NC group. The levels of plasma t-tau correlated significantly with the Montreal Cognitive Assessment (MoCA) and Boston naming test scores in the MCR group.

Conclusion

In this pilot study, we found significantly increased plasma t-tau proteins in the MCR and AD groups, compared with the NC group. The plasma t-tau levels were also significantly correlated with the cognitive function of older adults with MCR. These results implied that MCR and AD may share similar pathology. However, these findings need further confirmation in longitudinal studies.
Recommendation: Treatment of clinical long COVID encephalopathies with nasal administered mesenchymal stromal cell extracellular vesicles
Authors: Askenase Philip W.
Published: October 2022

We propose therapy with extracellular vesicles (EVs) for dominant central nervous system aspects of chronic Long COVID Syndromes (LCS). These clinical conditions have a delayed onset of 1–3 months following the cessation of active SARS-CoV-2 virus infections that cause an acute disease called COVID-19. The therapy of LCS will be achieved by direct access to the central nervous system (CNS) by nasal administration of small EVs derived from Mesenchymal Stromal Cells (MSC). When administered nasally, they target CNS microglia and endothelia involved in LCS encephalopathy, as indicated by experimental animal models and human autopsy and spinal fluid studies. Underlying this approach is the discovery that MSC-sEV treatment for healing neuro injury targets, microglia, and macrophages that then likely release secondary trophic EVs that affect the local capillary endothelial cells to restore vascular integrity. It is postulated that the pathways of endothelial and neural pathologies in acute SARS-CoV-2 virus infections may carry over to produce underlying vascular and neurological defects mediating LCS that are susceptible to this proposed nasal therapy with MSC-sEVs.
Self-decisive algorithm for unconstrained optimization problems as in biomedical image analysis
Authors: Jaffar Farah , Mashwani Wali Khan , Al-marzouki Sanaa Mohammed , Aamir Nudrat , Abiad Mohammad
Published: October 2022

This study describes the construction of a new algorithm where image processing along with the two-step quasi-Newton methods is used in biomedical image analysis. It is a well-known fact that medical informatics is an essential component in the perspective of health care. Image processing and imaging technology are the recent advances in medical informatics, which include image content representation, image interpretation, and image acquisition, and focus on image information in the medical field. For this purpose, an algorithm was developed based on the image processing method that uses principle component analysis to find the image value of a particular test function and then direct the function toward its best method for evaluation. To validate the proposed algorithm, two functions, namely, the modified trigonometric and rosenbrock functions, are tested on variable space.
Elevated expression of cholesterol transporter LRP-1 is crucially implicated in the pathobiology of glioblastoma
Authors: N. R. Shruthi , Behera Minakshi M. , Naik Sanoj Kumar , Das Sunil Kumar , Gopan Sooraj , Ghosh Amit , Sahu Rabi Narayan , Patra Susama , Purkait Suvendu
Published: October 2022

Glioblastoma (GBM) is the most common primary malignant brain tumor with a grave prognosis. The present study evaluated the expression of Cholesterol transporter [importer -Lipoprotein Receptor-related Protein-1 (LRP-1) and exporter -ATP-binding cassette transporters-1 (ABCA-1)] in GBM and their implications in tumor-biology, clinical outcome and therapeutic potentials. The mRNA and protein expression was assessed by qRT-PCR and immunohistochemistry, respectively, in 85 GBMs. For comparison, 25 lower-grade astrocytomas (IDH-mutant, grade-2/3) [LGA] 16 cases of high-grade astrocytomas (IDH-mutant, grade-4) [HGA] were also evaluated. In-vitro analysis was performed on U87MG and LN229 glioma cell line. The expression of LRP-1 (mRNA and protein) was significantly higher in GBM than LGA, HGA and normal brain (NB) [p-values 0.007, 0.003 and <0.001 for mRNA; 0.024, <0.001 and <0.001 for immunohistochemistry]. Majority of the GBMs (82.4%) showed strong immunoreactivity for LRP-1, and all tumor cases were positive while the normal brain was negative. LRP-1 immunoreactivity positively correlated with the MIB-1 labeling index (p-value-0.013). LRP-1 knockdown in-vitro was associated with decreased cell survival, proliferation, migration, invasion, and increased apoptosis. Similar effect was also demonstrated by Receptor Associated Protein (RAP), a LRP-1 inhibitory drug. The silencing of LRP-1 was also associated with decreased cholesterol level. The ABCA-1 expression was higher in GBM than LGA and NB (p-value 0.011 and <0.001), however there was no significant association with other parameters. LRP-1 showed a positive correlation with ABCA-1 and associated with decreased expression with LRP-1 knock-down in-vitro. The expression of LRP-1 and ABCA-1 didn't correlate with overall survival in GBMs. Hence, LRP-1 is crucial for the tumor cells' survival and aggressive biological behavior which is maintain through the regulation of high intracellular cholesterol import. Its expression is significantly higher in GBMs and also implicated in the regulation of ABCA-1 expression. Considering its immune-positivity only in the neoplastic cell and strong positivity in GBM it may be a useful adjunct to the diagnosis. For the first time, the present study emphasized its role as a potential therapeutic target in the form of RAP which is presently being used in other neurological diseases under clinical trials.
A non-immersive virtual reality-based intervention to enhance lower-extremity motor function and gait in patients with subacute cerebral infarction: A pilot randomized controlled trial with 1-year follow-up
Authors: Bian Minjie , Shen Yuxian , Huang Yijie , Wu Lishan , Wang Yueyan , He Suyue , Huang Dongfeng , Mao Yurong
Published: October 2022

Introduction

This study was conducted to evaluate whether a non-immersive virtual reality (VR)-based intervention can enhance lower extremity movement in patients with cerebral infarction and whether it has greater short-term and long-term effectiveness than conventional therapies (CTs).

Materials and methods

This was a single-blinded, randomized clinical controlled trial. Forty-four patients with subacute cerebral infarction were randomly allocated to the VR or CT group. All intervention sessions were delivered in the inpatient unit for 3 weeks. Outcomes were measured before (baseline) and after the interventions and at 3-month, 6-month and 1-year follow-ups. The outcomes included clinical assessments of movement and balance function using the Fugl–Meyer Assessment of Lower Extremity (FMA-LE) and Berg Balance Scale (BBS), and gait parameters in the sagittal plane.

Results

In the VR group, the walking speed after intervention, at 3-month, 6-month, and 1-year follow-ups were significantly greater than baseline (p= 0.01, <0.001, 0.007, and <0.001, respectively). Compared with baseline, BBS scores after intervention, at 3-month, 6-month, and 1-year follow-ups were significantly greater in both the VR group (p= 0.006, 0.002, <0.001, and <0.001, respectively) and CT group (p= <0.001, 0.002, 0.001, and <0.001, respectively), while FMA-LE scores after intervention, at 3-month, 6-month, and 1-year follow-ups were significant increased in the VR group (p= 0.03, <0.001, 0.003, and <0.001, respectively), and at 3-month, 6-month, and 1-year follow-ups in the CT group (p= 0.02, 0.004 and <0.001, respectively). In the VR group, the maximum knee joint angle in the sagittal plane enhanced significantly at 6-month follow-up from that at baseline (p= 0.04).

Conclusion

The effectiveness of the non-immersive VR-based intervention in our study was observed after the intervention and at the follow-ups, but it was not significantly different from that of CTs. In sum, our results suggest that non-immersive VR-based interventions may thus be a valuable addition to conventional physical therapies to enhance treatment efficacy.

Clinical trial registration

http://www.chictr.org.cn/showproj.aspx?proj=10541, ChiCTR-IOC-15006064.
Laminar functional magnetic resonance imaging in vision research
Authors: Demirayak Pinar , Deshpande Gopikrishna , Visscher Kristina
Published: October 2022

Magnetic resonance imaging (MRI) scanners at ultra-high magnetic fields have become available to use in humans, thus enabling researchers to investigate the human brain in detail. By increasing the spatial resolution, ultra-high field MR allows both structural and functional characterization of cortical layers. Techniques that can differentiate cortical layers, such as histological studies and electrode-based measurements have made critical contributions to the understanding of brain function, but these techniques are invasive and thus mainly available in animal models. There are likely to be differences in the organization of circuits between humans and even our closest evolutionary neighbors. Thus research on the human brain is essential. Ultra-high field MRI can observe differences between cortical layers, but is non-invasive and can be used in humans. Extensive previous literature has shown that neuronal connections between brain areas that transmit feedback and feedforward information terminate in different layers of the cortex. Layer-specific functional MRI (fMRI) allows the identification of layer-specific hemodynamic responses, distinguishing feedback and feedforward pathways. This capability has been particularly important for understanding visual processing, as it has allowed researchers to test hypotheses concerning feedback and feedforward information in visual cortical areas. In this review, we provide a general overview of successful ultra-high field MRI applications in vision research as examples of future research.
Dysregulation of prefrontal parvalbumin interneurons leads to adult aggression induced by social isolation stress during adolescence
Authors: Li Xinyang , Sun Huan , Zhu Yuanyuan , Wang Feidi , Wang Xiaodan , Han Lin , Cui Dongqi , Luo Danlei , Zhai Yifang , Zhuo Lixia , Xu Xiangzhao , Yang Jian , Li Yan
Published: October 2022

Social isolation during the juvenile stage results in structural and functional impairment of the brain and deviant adult aggression. However, the specific subregions and cell types that underpin this deviant behavior are still largely unknown. Here, we found that adolescent social isolation led to a shortened latency to attack onset and extended the average attack time, accompanied by anxiety-like behavior and deficits in social preference in adult mice. However, when exposed to social isolation during adulthood, the mice did not show these phenotypes. We also found that the structural plasticity of prefrontal pyramidal neurons, including the dendritic complexity and spine ratio, was impaired in mice exposed to adolescent social isolation. The parvalbumin (PV) interneurons in the prefrontal infralimbic cortex (IL) are highly vulnerable to juvenile social isolation and exhibit decreased cell numbers and reduced activation in adulthood. Moreover, chemogenetic inactivation of IL-PV interneurons can mimic juvenile social isolation-induced deviant aggression and social preference. Conversely, artificial activation of IL-PV interneurons significantly attenuated deviant aggression and rescued social preference during adulthood in mice exposed to adolescent social isolation. These findings implicate juvenile social isolation-induced damage to IL-PV interneurons in long-term aggressive behavior in adulthood.
Role of mitophagy in the neurodegenerative diseases and its pharmacological advances: A review
Authors: Wang Qixia , Xue Haoyuan , Yue Yundi , Hao Shiqi , Huang Shu-Hong , Zhang Zhaoqiang
Published: October 2022

Neurodegenerative diseases are a class of incurable and debilitating diseases characterized by progressive degeneration and death of cells in the central nervous system. They have multiple underlying mechanisms; however, they all share common degenerative features, such as mitochondrial dysfunction. According to recent studies, neurodegenerative diseases are associated with the accumulation of dysfunctional mitochondria. Selective autophagy of mitochondria, called mitophagy, can specifically degrade excess or dysfunctional mitochondria within cells. In this review, we highlight recent findings on the role of mitophagy in neurodegenerative disorders. Multiple studies were collected, including those related to the importance of mitochondria, the mechanism of mitophagy in protecting mitochondrial health, and canonical and non-canonical pathways in mitophagy. This review elucidated the important function of mitophagy in neurodegenerative diseases, discussed the research progress of mitophagy in neurodegenerative diseases, and summarized the role of mitophagy-related proteins in neurological diseases. In addition, we also highlight pharmacological advances in neurodegeneration.
IQSEC2-related encephalopathy in male children: Novel mutations and phenotypes
Authors: Liu Xinting , Zhang Shan , Wan Lin , Zhang Xiaoli , Wang Haiping , Zhang Hongwei , Zhu Gang , Liang Yan , Yan Huimin , Zhang Bo , Yang Guang
Published: October 2022

The isoleucine–glutamine (IQ) motif and Sec7 domain-containing protein 2 (IQSEC2) gene, located at Xp11. 2, are associated with nervous system diseases, such as epilepsy, autism, and intellectual disabilities. Gender-related differences in the severity of phenotype severity have been described previously. Here, we report the details of seven male children with IQSEC2 mutations from different families. During this investigation, we explored the relationship between the genotype and phenotype of IQSEC2 mutations; to do so, we recruited seven children with pathogenic/likely pathogenic IQSEC2 mutations who were diagnosed with global developmental delay and/or epilepsy. Their clinical features were assessed, and Trio-based whole-exome sequencing (trio WES) was conducted in seven pedigrees. A variety of algorithms and computational tools were used to calculate the pathogenicity, protein stability, conservation, side chain properties, and protein-protein interactions of mutated proteins. The seven patients ranged in age from 18 months to 5 years. Among them, six children were found to have both developmental delay and epilepsy, and one child only exhibited developmental delay. Four novel mutations (c.316C > T, c.443_4 44dup, c.3235T > C, and c.1417G > T) were newly reported. Two patients did not have truncated aberrant proteins caused by missense mutations. Still, they did have severe phenotypes, such as early-onset epilepsy in infancy, because the mutations were located in domains like the pleckstrin homology and IQ calmodulin-binding motif domains. The bioinformatics analysis also proved that missense mutations may be located in the functional region, which affects protein stability and is harmful. In summary, severe phenotypes, such as early-onset epilepsy in infancy, occur in male patients with a missense mutation in specific domains (e.g., pleckstrin homology and IQ calmodulin-binding motif domains). Some female individuals with IQSEC2 mutations may be asymptomatic because of the skewed inactivation of the X chromosome.