bluuebunny/crossref_metadata_2025 huggingface dataset:
Split phenomena in amyotrophic lateral sclerosis: Current evidences, pathogenetic hypotheses and diagnostic implications
Authors: Zoccolella Stefano , Giugno Alessia , Logroscino Giancarlo
Published: January 2023

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease and has emerged among the disorders with the largest increasing incidence in Western countries. Although the diagnosis is based on clinical grounds, electromyography (EMG), and nerve conduction studies (NCS) play a crucial role to exclude other potential etiologies of lower motor neuron (LMN) dysfunction. Based on clinical grounds, a peculiar pattern of dissociated atrophy of the intrinsic hand and foot muscles, termed the “split-hand” (SH) and “split-leg” (SL) signs, has been described in a significant proportion of subjects with ALS, even at the early stages of the disease, when symptoms are focal. These signs are rare in neurological and non-neurological diseases other than ALS. In this review, we discussed current evidences concerning SH and SL signs, their pathogenetic hypotheses and neurophysiological findings. We also analyze whether SH and SL signs can be reliable markers in the differential diagnosis and in the prognosis of ALS.
Frequency-dependent functional alterations in people living with HIV with early stage of HIV-associated neurocognitive disorder
Authors: Wang Wei , Liu Dan , Wang Yuanyuan , Li Ruili , Liu Jiaojiao , Liu Mingming , Wang Huasong , Li Hongjun
Published: January 2023

Background

HIV enters the brain soon after seroconversion and causes HIV-associated neurocognitive disorder (HAND). However, the pathogenesis of this insidious impairment at an early stage remains unclear.

Objectives

To explore functional integration and segregation changes at the early stages of HAND, voxel-level indices of regional homogeneity (ReHo), the amplitude of low-frequency fluctuations (ALFF), and voxel-mirrored homotopic connectivity (VMHC) under two different frequency bands (slow-5: 0.01–0.027 Hz; slow-4: 0.027–0.073 Hz) were analyzed.

Methods

Ninety-eight people living with HIV (PLWH) and 44 seronegative controls underwent resting-state functional magnetic resonance imaging. Furthermore, all PLWHs underwent neuropsychological and daily functioning tests. The main effect of the group and the interaction between the group and frequency band were investigated. Finally, the relationship between the altered indices and the cognitive domains was explored.

Results

A significant group-by-frequency interaction was demonstrated in the right thalamus for ReHo; for VMHC, the interaction was observed in the bilateral precuneus and paracentral gyrus. The post hoc Bonferroni test indicated that the alteration of ReHo and VMHC could only be detected in slow-5. PLWH showed significantly reduced ALFF in both the frequency bands in the right occipital gyrus and right calcarine. Moreover, some altered functional integration and segregation indices are related to impaired cognitive function.

Conclusion

People living with HIV displayed aberrant functional integration and segregation at the early stages of HAND, which is linked to cognitive function. The frequency band of slow-5 might be more sensitive for detecting insidious damage at an early stage.
Almond intake alters the acute plasma dihydroxy-octadecenoic acid (DiHOME) response to eccentric exercise
Authors: Nieman David C. , Omar Ashraf M. , Kay Colin D. , Kasote Deepak M. , Sakaguchi Camila A. , Lkhagva Ankhbayar , Weldemariam Mehari Muuz , Zhang Qibin
Published: January 2023

Introduction

This investigation determined if 4-weeks ingestion of nutrient-dense almonds mitigated post-exercise inflammation and muscle soreness and damage.

Methods

An acute 90-min of eccentric exercise (90-EE) was used to induce muscle damage in 64 non-obese adults not engaging in regular resistance training (ages 30–65 years, BMI < 30 kg/m2). Using a parallel group design, participants were randomized to almond (AL) (57 g/d) or cereal bar (CB) (calorie matched) treatment groups for a 4-week period prior to the 90-EE (17 exercises). Blood and 24-h urine samples were collected before and after supplementation, with additional blood samples collected immediately post-90-EE, and then daily during 4 additional days of recovery. Changes in plasma oxylipins, urinary gut-derived phenolics, plasma cytokines, muscle damage biomarkers, mood states, and exercise performance were assessed.

Results

The 90-EE protocol induced significant muscle damage, delayed onset of muscle soreness (DOMS), inflammation, reduced strength and power performance, and mood disturbance. Interaction effects (2 group × 7 time points) supported that AL vs. CB was associated with reduced post-exercise fatigue and tension (p = 0.051, 0.033, respectively) and higher levels of leg-back strength (p = 0.029). No group differences were found for post-90-EE increases in DOMS and six cytokines. AL was associated with lower levels of serum creatine kinase immediately- and 1-day post-exercise (p = 0.034 and 0.013, respectively). The 90-EE bout increased plasma levels immediately post-exercise for 13 oxylipins. Interaction effects revealed significantly higher levels for AL vs. CB for 12,13-DiHOME (p < 0.001) and lower levels for 9,10-DiHOME (p < 0.001). Urine levels increased in AL vs. CB for seven gut-derived phenolics including 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone that was inversely related to changes in plasma 9,10-DiHOME (r = −0.029, p = 0.021).

Discussion

These data support some positive effects of almond intake in improving mood state, retaining strength, decreasing muscle damage, increasing the generation of gut-derived phenolic metabolites, and altering the plasma oxylipin DiHOME response to unaccustomed eccentric exercise in untrained adults. The elevated post-exercise plasma levels of 12,13-DiHOME with almond intake support positive metabolic outcomes for adults engaging in unaccustomed eccentric exercise bouts.
Influence of Lactobacillus helveticus ZF22 and TR1-1-3 strains on the aromatic flavor of fermented sausages
Authors: Tian Jianjun , Yang Xueqian , Zhang Kaiping , Zhao Yanhong , Cheng Feng , Jin Ye
Published: January 2023

In this study, five strains isolated from traditional Inner Mongolian air-dried meat products were used, two Lactobacillus helveticus strains, ZF22 and TR1-1-3, with potent antibacterial activity, acid, salt, and nitrite tolerance, were selected for this study. Lactic acid bacteria (LAB) (Lactobacillus helveticus ZF22 and TR1-1-3) were inoculated into fermented sausages at 107 CFU/g and their volatiles were studied during fermentation and storage. Clustering heat map and principal component analysis (PCA) were used to identify differentiating flavor components in uninoculated and inoculated sausages. The results showed that 72 volatile flavor substances were identified during the fermentation of the fermented sausages and that inoculation with Lactobacillus helveticus ZF22 and TR1-1-3 increased the proportion of acids, ketones and alkanes. Moreover, the clustering heat map demonstrated that esters such as ethyl isobutyrate, ethyl acetate, and ethyl valerate were more abundant in TR1-1-3 and ZF22 than ZR. The PCA analysis showed that the volatile compounds of the three fermented sausages were distributed in separate quadrants, suggesting that the volatile compound compositions of the three fermented sausages differed significantly. Our findings suggest that inoculating fermented sausages with Lactobacillus helveticus TR1-1-3 and ZF22 can improve flavor by enhancing the type and amount of flavor compounds.
Natural deep eutectic solvent-ultrasound assisted extraction: A green approach for ellagic acid extraction from Geum japonicum
Authors: Yang Zhao , Yue Shi-Jun , Gao Huan , Zhang Qiao , Xu Ding-Qiao , Zhou Jing , Li Jia-Jia , Tang Yu-Ping
Published: January 2023

Introduction

In China and other Asian nations, Geum japonicum (GJ) is used as functional vegetables or as a type of folk medicine. Ellagic acid (EA) is one of the main active ingredients in GJ and has been utilized in food, cosmetics, and medicinal goods worldwide. Natural deep eutectic solvents (NADESs) have gradually replaced organic solvents for efficient extraction of plant-derived active compounds due to its environmental protection, low toxicity, low solubility, reusability, etc.

Methods

NADES with the highest EA yield was selected and the extraction conditions were optimized by response surface methodology (RSM), the antioxidant activity of NADES extract was determined, and finally Fourier transform infrared (FT-IR) and scanning electron microscopy (SEM) were used to explain the mechanism for the increase of EA yield in GJ.

Results

In this work, several NADESs were tailored for the ultrasound assisted extraction (UAE) of EA from GJ, among which choline chloride-oxalic acid (ChCl:Oa) was the most effective. In optimal conditions, ChCl:Oa extract produced higher EA yields than common organic solvents including methanol, ethanol, and acetone. In vitro antioxidant experiments showed that ChCl:Oa extract had stronger DPPH radical scavenging ability than other solvent extracts. Mechanically, FT-IR results indicated that ChCl:Oa could form a hydrogen bonding with EA, which enhanced the stability of EA. Meanwhile, ChCl:Oa-UAE treatment could destroy the tissue structure of GJ, thereby improving EA yield.

Discussion

In conclusion, these results imply that the ChCl:Oa-UAE method might be an environmentally friendly approach for extracting EA from GJ.
Anti-inflammatory effects and molecular mechanisms of bioactive small molecule garlic polysaccharide
Authors: Shao Xin , Li Jialong , Zhang Huidan , Zhang Xuhui , Sun Chongzhen , Ouyang Xin , Wang Yong , Wu Xiyang , Chen Chunbo
Published: January 2023

Although garlic polysaccharides have been found to possess anti-inflammatory activities, anti-inflammatory study on small molecule water-soluble garlic polysaccharide (WSGP) is few. In this study, a novel WSGP with a molecular weight of 1853 Da was isolated by DEAE-52 and Sephadex G-100 column and the chemical composition was identified by monosaccharide composition and methylation analysis. Furthermore, the antioxidant effects of WSGP and the potential molecular mechanisms on LPS-induced inflammatory responses in RAW264.7 macrophage cells were investigated. The results showed that WSGP has strong antioxidant activity, such as DPPH, hydroxyl, superoxide anion, ABTS radical scavenging capacity, Fe2+ chelating ability and reducing power. Meanwhile, WSGP could considerably suppress the manufacturing of NO and the mRNA and protein expression degrees of IL-6, TNF-α, and IL-1β in LPS inspired RAW264.7 macrophages WSGP could significantly suppress the production of NO and the mRNA and protein expression levels of IL-1β, IL-6, and TNF-α in LPS stimulated RAW264.7 macrophage cells (p < 0.05). In addition, the phosphorylated IκB-α, p65, and STAT3 proteins were significantly increased in LPS-induced macrophages, while this trend was significantly reversed by WSGP treatment in a concentration-dependent manner (p < 0.05). Consequently, WSGP supplementation might reduce LPS-induced inflammatory responses by suppressing proinflammatory cytokines and NF-κB and STAT3 pathway activation. The finding of this research would give scientific guidelines for the judicious use of small molecular garlic polysaccharide in anti-inflammatory treatments.
Storage stability of texture, organoleptic, and biological properties of goat milk yogurt fermented with probiotic bacteria
Authors: Yang Yaling , Zhang Ruyue , Zhang Fuxin , Wang Bini , Liu Yufang
Published: January 2023

Introduction

Goat milk is an attractive food due to its high nutritional values, easy digestibility and hypoallergenicity, but has an undesirable “goaty” flavor.

Methods

In this study, goat yogurt was fermented with four probiotics, respectively, including Lactobacillus acidophilus (GYA), Bifidobacterium animalis (GYB), Lactobacillus casei (GYC) and Lactobacillus plantarum (GYP), and tested for texture, organoleptic, and biological properties during a 4-week storage period at the refrigerated temperature.

Results

All goat yogurt with probiotics showed an increase on titratable acidity and a corresponding downward trend on pH value. Viable counts of L. acidophilus and L. casei were above 6 log cfu/mL at the end of the storage, which met the minimum standards for viable probiotic bacteria in yogurt specified by the Food and Agriculture Organization of United Nation (FAO). The texture and organoleptic characteristics of fermented goat milk depended on the strain and the storage period. DPPH free radical scavenging rate and ferric reducing antioxidant power activity gradually increased in all goat yogurts during the storage and yogurt with probiotic bacteria showed higher values than those of GY0.

Discussion

Among all probiotic containing goat yogurts, GYC exhibited the desirable characteristics of hardness, adhesiveness, water holding capacity, antioxidant activity during the whole storage. Furthermore, the addition of L. casei effectively weakened the goaty flavor and enhanced the overall acceptability. Thus, fermented goat milk with L. casei is optional for the development of goat milk product with satisfactory texture properties, pleasant sensory quality and high bioactivity.
Quality assessment of pre- and postnatal nutrition and exercise mobile applications in the United States and China
Authors: Yu Hongli , He Juan , Li Keqiang , Qi Wen , Lin Jiahui , Szumilewicz Anna
Published: January 2023

Background

Mobile applications (apps) are becoming increasingly prevalent as tools for improving maternal health behaviors. However, the recently updated content and quality of these apps remain unknown. This research investigated the fundamental characteristics, functional modules, and overall quality of maternal apps available in the United States and China to reveal critical nutrition and physical activity gaps.

Methods

A systematic search was performed in Android and iOS app stores (China and the United States). Apps were eligible if they targeted pregnant or postpartum women, focused on nutrition or physical activity, and had interfaces in English or Chinese. The basic characteristics, functional modules, and overall quality of the apps were evaluated, and differences between apps available in China or the United States were determined using analysis of variance and chi-square tests. Pearson correlations were utilized to investigate links between objective quality and user rating.

Results

A total of 65 maternity-related nutrition and physical activity apps (34 from China and 31 from the United States) were eligible. Among them, 68% (21/31) of US apps and 56% (19/34) of Chinese apps did not provide supporting evidence for their content. A greater number of Chinese apps provided app-based general education modules, namely food nutrition knowledge (n = 0, 0% in the United States vs. n = 30, 88.2% in China). Meanwhile, a greater number of US apps provided exercise modules, namely pregnancy yoga (n = 21, 67.7% in the United States vs. n = 2, 5.9% in China). The overall app quality rating in the United States was lower than it was in China (mean: 3.5, SD: 0.6 in China vs. mean: 3.4, SD: 0.7 in the United States). There was no relationship between the overall app quality rating and the user rating in either country (rho = 0.11 in China and rho = –0.13 in the United States).

Conclusion

The characteristics and functional modules of in-store apps for maternal nutrition and physical activity differed between the United States and China. Both countries’ apps, especially Chinese apps, lacked evidence-based information, and there was no correlation between app quality and user rating. The results therefore suggest that user ratings cannot be used as an objective indicator of app quality and that it is necessary to improve the empirical basis and credibility of apps in both countries.
Undifferentiated hepatic carcinoma with osteoclast-like giant cells: A case report and literature review
Authors: Deng Yujiao , Wang Ya , Zhang Yan , Yang Na , Ji Xingli , Wu Bing
Published: January 2023

Osteoclast-like giant cell tumor (OGCT) is a common bone tumor, occasionally observed in some extraosseous organs, but rarely involving the digestive system, especially the liver. Previously reported osteoclast-like giant cell carcinoma of the liver often coexists with sarcomatoid or hepatocellular carcinoma. Undifferentiated liver tumors with osteoclast-like giant cells (OGCs) are extremely rare. Due to its rarity, there is no consensus for diagnosis and treatment of undifferentiated liver tumors with OGCs. Definitive diagnosis comes from surgery, so there is often a long delay in diagnosis following the occurrence of symptoms. This case describes an extremely rare case of an undifferentiated liver tumor with OGCs in detail. It also summarizes the previously published cases based on liver tumors with OGCs from August 1980 to June 2021, providing extensive evidence to improve preoperative diagnosis and management options.
Research landscape and trends of melanoma immunotherapy: A bibliometric analysis
Authors: Liu Yanhao , Yu Lan , Liang Yanjiao , Cheng Xi , Jiang Shu , Yu Haiming , Zhang Zhen , Lu Linlin , Qu Baozhen , Chen Yuxian , Zhang Xiaotao
Published: January 2023

Background

Immunotherapy for lung cancer has been a hot research area for years. This bibliometric analysis was intended to present research trends on melanoma immunotherapy.

Method

On April 1, 2022, the authors identified 2,109 papers on melanoma immunotherapy using the Web of Science and extracted their general information and the total number of citations. The authors then conducted a bibliometric analysis to present the research landscape, clarify the research trends, and determine the most cited papers (top-papers) as well as major journals on melanoma immunotherapy. Subsequently, recent research hotspots were identified by analyzing the latest articles in major journals.

Results

The total and median number of citations of these 2,109 papers on melanoma immunotherapy was 137,686 and 11, respectively. “Improved survival with ipilimumab in patients with metastatic melanoma” by Hodi et al. was the most cited paper (9,824 citations). Among the journals, the top-paper number (16), average citations per paper (2,510.7), and top-papers rate (100%) of New England Journal of Medicine were the highest. Corresponding authors represented the USA took part in most articles (784). Since 2016, the hottest research area has changed from CTLA-4 to PD-1.

Conclusions

This bibliometric analysis comprehensively and quantitatively presents the research trends and hotspots based on 2,109 relevant publications, and further suggests future research directions. The researchers can benefit in selecting journals and in finding potential collaborators. This study can help researchers gain a comprehensive impression of the research landscape, historical development, and current hotspots in melanoma immunotherapy and can provide inspiration for future research.
Cardiac toxicity in patients with lung cancer receiving thoracic radiotherapy and immunotherapy
Authors: Son Christine , Moey Melissa Y. Y. , Walker Paul R. , Naqash Abdul R. , Peach Matthew Sean , Ju Andrew W.
Published: January 2023

Background

Immune checkpoint inhibitors (ICIs) are used to treat locally-advanced and metastatic lung cancer, which can lead to severe immunogenic-related cardiotoxicities. We assessed the risk of cardiotoxicity in ICI-treated lung cancer patients with or without cardiac radiation from thoracic radiotherapy.

Methods

Retrospective data was collected on Stage III-IV lung cancer patients who received ICIs between 2015 and 2018. All cardiotoxicities associated with ICI were assessed in correlation with the timing of radiotherapy (RT) in relation to ICI, and the mean RT heart dose. The rate of cardiac events in relation to RT timing and heart dose was compared using multiple logistic regression including the Framingham risk score and steroid use prior to ICI therapy.

Results

Of 194 ICI-treated patients evaluated, 55.2% (n=107/194) patients had received thoracic RT at a median dose of 60.4 Gy (range, 15-75). Cardiotoxicities such as non-ST elevated myocardial infarction and new onset supraventricular tachycardias were observed in 13 (12.2%) of those who had thoracic RT versus 9 (10.3%) who did not (p=0.87). 38 patients who received RT concurrently with ICI did not develop any cardiotoxicity whereas 14.1% (n=22/156) of those who did not receive concurrent RT developed cardiotoxicities (univariate, p=0.030; multivariate, p=0.055). There were no significant differences in the mean heart RT dose, Framingham risk score, and steroid treatment between patients that received concurrent RT with ICI versus non-concurrent RT/ICI.

Conclusion

ICI-related cardiotoxicities were not significantly associated with patients who received concurrent thoracic radiotherapy in this retrospective review. Further validation of prospective studies is needed to confirm these results.
Prophylactic doxazosin reduces urinary retention and promotes recovery after total joint arthroplasty: A randomized controlled trial
Authors: Ding Zichuan , Cao Jian , Huang Chao , Zhou Kai , Wang Haoyang , Zhou Zongke
Published: January 2023

Background: Postoperative urinary retention (POUR) is a common and disruptive complication following total joint arthroplasty (TJA). The aim of this study is to investigate whether doxazosin can decrease the incidence of POUR and promote recovery under the setting of modern enhanced recovery after TJA.

Methods: In this randomized placebo-controlled trial, patients over 35 years of age undergoing primary unilateral TJA were recruited. Patients received doxazosin (4 mg once) or placebo 2 h before surgery. The primary outcome of interest was the development of POUR, which was diagnosed when patients with a urine volume over 400 ml or overflow incontinence. Postoperative recovery was assessed in terms of hospital length of stay after surgery, daily ambulation distance, visual analogue scale (VAS) pain score and opioid consumption.

Results: A total of 170 male patients were equally randomized into Doxazosin group (mean age 54.2 ± 13.7 years, range 36–88 years) and Placebo group (mean age 54.6 ± 13.9 years, range 38–81 years). The POUR rate was significant lower in Doxazosin group (17.6%) than in Placebo group (36.5%) (p = .006). The mean LOS in the Doxazosin group was 3.1 ± 1.1 days compared to 3.6 ± 1.7 days in the Placebo group (p = .030). Doxazosin group had a longer daily mobilization distance than Placebo group on postoperative day 1 (26.8 ± 11.1 vs. 22.8 ± 9.7; p = .015). Postoperative pain assessed by VAS score and opioid usage was comparable between two groups.

Conclusion: Our results support the routine use of prophylactic doxazosin in male patients to decrease POUR rate and promote postoperative recovery under the setting of modern enhanced recovery after TJA.
Population pharmacokinetics and dose evaluations of linezolid in the treatment of multidrug-resistant tuberculosis
Authors: Zhang Haoyue , He Yuying , Davies Forsman Lina , Paues Jakob , Werngren Jim , Niward Katarina , Schön Thomas , Bruchfeld Judith , Alffenaar Jan-Willem , Hu Yi
Published: January 2023

Background: The pharmacokinetic/pharmacodynamics (PK/PD) target derived from the hollow-fiber system model for linezolid for treatment of the multidrug-resistant tuberculosis (MDR-TB) requires clinical validation. Therefore, this study aimed to develop a population PK model for linezolid when administered as part of a standardized treatment regimen, to identify the PK/PD threshold associated with successful treatment outcomes and to evaluate currently recommended linezolid doses.

Method: This prospective multi-center cohort study of participants with laboratory-confirmed MDR-TB was conducted in five TB designated hospitals. The population PK model for linezolid was built using nonlinear mixed-effects modeling using data from 168 participants. Boosted classification and regression tree analyses (CART) were used to identify the ratio of 0- to 24-h area under the concentration-time curve (AUC0-24h) to the minimal inhibitory concentration (MIC) threshold using the BACTEC MGIT 960 method associated with successful treatment outcome and validated in multivariate analysis using data from a different and prospective cohort of 159 participants with MDR-TB. Furthermore, based on the identified thresholds, the recommended doses were evaluated by the probability of target attainment (PTA) analysis.

Result: Linezolid plasma concentrations (1008 samples) from 168 subjects treated with linezolid, were best described by a 2-compartment model with first-order absorption and elimination. An AUC0–24h/MIC > 125 was identified as a threshold for successful treatment outcome. Median time to sputum culture conversion between the group with AUC0-24h/MIC above and below 125 was 2 versus 24 months; adjusted hazard ratio (aHR), 21.7; 95% confidence interval (CI), (6.4, 72.8). The boosted CART-derived threshold and its relevance to the final treatment outcome was comparable to the previously suggested target of AUC0–24h/MIC (119) using MGIT MICs in a hollow fiber infection model. Based on the threshold from the present study, at a standard linezolid dose of 600 mg daily, PTA was simulated to achieve 100% at MGIT MICs of ≤ .25 mg which included the majority (81.1%) of isolates in the study.

Conclusion: We validated an AUC0–24h/MIC threshold which may serve as a target for dose adjustment to improve efficacy of linezolid in a bedaquiline-containing treatment. Linezolid exposures with the WHO-recommended dose (600 mg daily) was sufficient for all the M. tb isolates with MIC ≤ .25 mg/L.
Beta-blockers in cardiac arrhythmias–Clinical pharmacologist’s point of view
Authors: Wołowiec Łukasz , Grześk Grzegorz , Osiak Joanna , Wijata Aleksandra , Mędlewska Martyna , Gaborek Patryk , Banach Joanna , Wołowiec Anna , Głowacka Mariola
Published: January 2023

β-blockers is a vast group of antiarrhythmic drugs which differ in their pharmacokinetic and chemical properties. Some of them block β-adrenergic receptors selectively while the others work non-selectively. Consequently, they reduce the influence of the sympathetic nervous system on the heart, acting negatively inotropic, chronotropic, bathmotropic and dromotropic. Although they have been present in medicine since the beginning of the 1960s, they still play a crucial role in the treatment of cardiac arrhythmias. They are also first-line group of drugs used to control the ventricular rate in patients with the most common arrhythmia–atrial fibrillation. Previous reports indicate that infection with SARS-CoV-2 virus may constitute an additional risk factor for arrhythmia. Due to the aging of the population in developed countries and the increase in the number of patients with cardiac burden, the number of people suffering from cardiac arrhythmias will increase in the upcoming years. As a result the role of above-mentioned beta-blockers will remain significant. Particularly noteworthy is propranolol–the oldest beta adrenergic antagonist, which in recent years has found additional applications due to its unique properties. In this article, we reviewed the accessible literature and summarized the current guidelines on the use of beta-blockers in the treatment of cardiac arrhythmias.
Hyperuricaemia, gout and related adverse events associated with antihypertensive drugs: A real-world analysis using the FDA adverse event reporting system
Authors: Jiao Xue-Feng , Song Kunpeng , Jiao Xueyan , Li Hailong , Zeng Linan , Zou Kun , Zhang Wei , Wang Huiqing , Zhang Lingli
Published: January 2023

Background: The role of antihypertensive drugs in inducing hyperuricaemia and gout has been a long-term concern in clinical practice. However, clinical studies regarding this issue are limited in number and have yielded inconsistent results. We comprehensively evaluated the association between various antihypertensive drugs and the occurrences of hyperuricaemia, gout and related adverse events (AEs) using the FDA Adverse Event Reporting System (FAERS), aiming to guide the selection of antihypertensive drugs with a goal of minimizing the risk of hyperuricaemia, gout and related AEs.

Methods: We used OpenVigil 2.1 to query the FAERS database. Hyperuricaemia, gout and related AEs were defined by 5 Preferred Terms: hyperuricaemia, gout, gouty arthritis, gouty tophus and urate nephropathy. Disproportionality analysis was performed, and a positive signal indicated an association between AEs and antihypertensive drugs.

Results: The numbers of antihypertensive drugs with positive signals for hyperuricaemia, gout, gouty arthritis, gouty tophus and urate nephropathy were 46, 66, 27, 8 and 6, respectively. These drugs included diuretics, antihypertensive drugs with central action, α blockers, β blockers, α and β blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, renin inhibitors, vasodilators, and compound preparations. Furthermore, 42 antihypertensive drugs had positive signal for more than one AEs.

Conclusion: Our study suggests that some potassium-sparing diuretics, calcium channel blockers and losartan may be associated with increased risk of hyperuricaemia, gout or related AEs, which is inconsistent with most previous studies. Moreover, Our study also suggests that some antihypertensive drugs with central action, α and β blockers, renin inhibitors and vasodilators may be associated with increased risk of hyperuricaemia, gout or related AEs, which has not been reported in previous studies. These findings complement real-world evidence on the potential risks of hyperuricaemia, gout and related AEs associated with antihypertensive drugs.
Study on the mechanism of action of Scutellaria barbata on hepatocellular carcinoma based on network pharmacology and bioinformatics
Authors: Yang An-Yin , Liu Hong-Li , Yang Yong-Feng
Published: January 2023

Background: Hepatocellular carcinoma is one of the most common cancers with the characteristics of invasion and high mortality. Current forms of prevention remain severe. Scutellaria barbata is widely used in traditional Chinese medicine treatment of various tumors. This study explored the mechanism of Scutellaria barbata in the treatment of hepatocellular carcinoma by network pharmacology and bioinformatics.

Methods: The active ingredients of Scutellaria barbata and potential targets for the treatment of hepatocellular carcinoma were collected by network pharmacology. The protein interaction network was constructed to screen the core targets, and the association between the core targets and diseases was further verified by bioinformatics methods. Finally, the active ingredients corresponding to the targets closely related to the disease were screened for AMDE characteristics analysis. Molecular docking of drug-like ingredients with corresponding targets was performed. We used CCK-8 kit to determine the effect of active ingredients on cell proliferation.

Results: 29 candidate active ingredients and 461 related targets of Scutellaria barbata were screened. A total of 8238 potential therapeutic targets for hepatocellular carcinoma were indentified. Finally, 373 potential targets for the treatment of HCC were obtained. The active ingredients: wogonin, Rhamnazin, eriodictyol, quercetin, baicalein, and luteolin, etc. The core targets were CDK1, CDK4, SRC, and E2F1. A total of 3056 GO enrichment entries were obtained, and 180 enrichment results were obtained by KEGG pathway analysis. Genes were mainly enriched in PI3K-Akt signaling pathway, IL-17 signaling pathway, TNF signaling pathway, apoptosis pathway, and hepatocellular carcinoma pathway. Molecular docking results showed that the screened compounds had strong binding ability with the corresponding target proteins. CCK8 assays showed that Rhamnazin and Luteolin suppressed the proliferation of HCC cells significantly compared with controls.

Conclusion: This study revealed that the mechanism of Scutellaria barbata in the treatment of hepatocellular carcinoma may be that the active ingredients inhibit the expression of core genes and block the PI3K-AKT signaling pathway to inhibit the proliferation, and migration and induce apoptosis of cancer cells.
Inhibitory effect of main phenolic acid components of Jacobaea cannabifolia (Less.) on inflammation caused by PM2.5
Authors: Xu Bao-Li , Wang Yuan-Yuan , Jiang Ling-Ling , Liu Zhen , Liu Ding-Rui , Zhao He , Li Shi-Liang , Wang Xiao-Bo
Published: January 2023

PM2.5 is an important environmental problem threatening human health at present, which poses serious harm to human body after inhalation. J. cannabifolia is a traditional Chinese medicine which exhibits anti-inflammatory effect. This study aimed to investigate the inhibitory effect of main phenolic acid components of J. cannabifolia on inflammation caused by PM2.5. Effect of PM2.5 on cell activity and apoptosis were determined by MTT, flow cytometry and calcein AM/PI staining. PHBA, PHPAA, and mixture of PHBA and PHPAA of different concentrations were given to RAW264.7 cells pretreated with PM2.5. The effect of drugs on cellular inflammatory factors was detected by ELISA. The expressions of TLRs related signal pathway at protein and gene levels were detected by western blot and qRT-PCR. The results showed that PM2.5 had no effect on cell activity and apoptosis within the determined concentration range. PHBA and PHPAA could markly inhibit the level of IL-1β, IL-6, and TNF-α in RAW264.7 cells. Furthermore, the expressions of TLR2, TLR4, MyD88, IRAK1, TRAF6, TAK1, IKKβ, and NF-κB induced by PM2.5 were markedly inhibited by PHBA and PHPAA at protein and gene levels. This study demonstrated that PHBA and PHPAA could attenuated inflammation caused by PM2.5 through suppressing TLRs related signal pathway.
Role of M1 macrophages in diabetic foot ulcers and related immune regulatory mechanisms
Authors: Li Yao , Li Xiaoyan , Ju Shuai , Li Wenqiang , Zhou Siyuan , Wang Guili , Cai Yunmin , Dong Zhihui
Published: January 2023

Objectives: Diabetes foot ulcers (DFUs) are characterized by immune infiltration of M1 macrophages observed in foot skin, in which immune-associated genes (IRGs) play a prominent role. The precise expression of IRGs as well as any possible regulatory mechanisms that could be present in DFUs is yet unknown.

Methods: The sequencing data of single-cell RNA (scRNA) in the foot skin of patients with DFUs were analyzed, screening out the cluster marker genes of foot skin obtained from the ImmPort database. IRG activity was assessed with the AUCell software package. The IRGs of DFUs were explored by analyzing the batch sequencing dataset of DFU skin tissue. HumanTFDB was adopted to identify relevant regulatory transcription factors (TFs). The STRING dataset was used to build the main TF protein–protein interaction networks. WB and immunofluorescence methods were used to verify M1 macrophage-related immune regulators.

Results: There were 16 clusters found: SMC1, fibro, t-lympho, he fibro, vasendo, baselkera, diffkera, SMC2, M1 macro, M2 macro, sweet/seba, B-Lympho, Melanio, lymphendo, plasma, and Schwann. M1 and M2 macrophages both had considerably higher AUC ratings than patients with DFUs compared to other sub-populations of cells. The proportion of M1 macrophages was the highest in the non-healing group. According to scRNA analysis and batch sequencing data by GO and KEGG, DEGs were enriched in immune response. Some 106 M1 macro-IRGs were finally identified and 25 transcription factors were revealed as associated with IRG expression. The PPI network indicated NFE2L2, REL, ETV6, MAF, and NF1B as central transcription factors.

Conclusion: Based on the bio-informatics analysis of scRNA and high-throughput sequencing data, we concluded that M1 macrophages may serve as the influencing factor of DFUs’ non-union. In addition, NFE2L2 could be involved in the regulation of IRG expression within M1 macrophages.
Rhein for treating diabetes mellitus: A pharmacological and mechanistic overview
Authors: Deng Tingting , Du Jinxin , Yin Ying , Cao Baorui , Wang Zhiying , Zhang Zhongwen , Yang Meina , Han Jinxiang
Published: January 2023

With the extension of life expectancy and changes in lifestyle, the prevalence of diabetes mellitus is increasing worldwide. Rheum palmatum L. a natural botanical medicine, has been used for thousands of years to prevent and treat diabetes mellitus in Eastern countries. Rhein, the main active component of rhubarb, is a 1, 8-dihydroxy anthraquinone derivative. Previous studies have extensively explored the clinical application of rhein. However, a comprehensive review of the antidiabetic effects of rhein has not been conducted. This review summarizes studies published over the past decade on the antidiabetic effects of rhein, covering the biological characteristics of Rheum palmatum L. and the pharmacological effects and pharmacokinetic characteristics of rhein. The review demonstrates that rhein can prevent and treat diabetes mellitus by ameliorating insulin resistance, possess anti-inflammatory and anti-oxidative stress properties, and protect islet cells, thus providing a theoretical basis for the application of rhein as an antidiabetic agent.
Comparison of translational and rotational modes towards passive rheology of the cytoplasm of MCF-7 cells using optical tweezers
Authors: Roy Srestha , Vaippully Rahul , Lokesh Muruga , Nalupurackal Gokul , Edwina Privita , Bajpai Saumendra , Roy Basudev
Published: January 2023

A colloidal particle placed inside the cell cytoplasm is enmeshed within a network of cytoskeletal fibres immersed in the cytosolic fluid. The translational mode is believed to yield different rheological parameters than the rotational mode, given that these modes stretch the fibers differently. We compare the parameters for Michigan Cancer Foundation-7 (MCF-7) cells in this manuscript and find that the results are well comparable to each other. At low values of 0 Hz viscosity, the rotational and translational viscoelasticity matches well. However, discrepancies appear at higher values which may indicate that the cytoskeletal modes involved in rotation and translation of the particle are getting invoked. We also show that the 0 Hz viscosity increases as the cell ages under the conditions of constant room temperature of 25°C on the sample chamber.
Photoelectron momentum distributions with twisted attosecond X waves carrying orbital angular momentum
Authors: Zhang Xiaofan , Ma Xiaomeng
Published: January 2023

We theoretically investigate the photoelectron momentum distributions of 1s and 2px,y states of hydrogen by twisted attosecond X waves carrying orbital angular momentum based on first-order perturbation theory. The photoionization spectra as a function of photoelectron energy and emission angle are analyzed respectively. The results indicate that there are interference fringes in the energy spectra and more nodes in the angular distributions. These angular nodes are attributed to both orbital structure and the temporal-spatial structure of X waves. We derive an equation that can quantitatively describe the angular nodes in the photoelectron angular distributions. Our results and analyses indicate that the angular distribution is an important observation for the investigation of the information of both orbitals and X waves.
Morphogenesis of the gastrovascular canal network in Aurelia jellyfish: Variability and possible mechanisms
Authors: Song Solène , Żukowski Stanisław , Gambini Camille , Dantan Philippe , Mauroy Benjamin , Douady Stéphane , Cornelissen Annemiek J. M.
Published: January 2023

Patterns in biology can be considered as predetermined or arising from a self-organizing instability. Variability in the pattern can, thus, be interpreted as a trace of instability, growing out from noise. Studying this variability can, thus, hint toward an underlying morphogenetic mechanism. Here, we present the variability of the gastrovascular system of the jellyfish Aurelia. In this variability emerges a typical biased reconnection between canals and time-correlated reconnections. Both phenomena can be interpreted as traces of mechanistic effects, the swimming contractions on the tissue surrounding the gastrovascular canals, and the mean fluid pressure inside them. This reveals the gastrovascular network as a model system to study the morphogenesis of circulation networks and the morphogenetic mechanisms at play.
Spindle wave in intracranial pressure signal analysis for patients with traumatic brain injury: A single-center prospective observational cohort study
Authors: Zhu Jun , Shan Yingchi , Li Yihua , Liu Jiaqi , Wu Xiang , Gao Guoyi
Published: January 2023

Objective: Intracranial pressure (ICP) monitoring is an integral part of the multimodality monitoring system in the neural intensive care unit. The present study aimed to describe the morphology of the spindle wave (a shuttle shape with wide middle and narrow ends) during ICP signal monitoring in TBI patients and to investigate its clinical significance.

Methods: Sixty patients who received ICP sensor placement and admitted to the neurosurgical intensive care unit between January 2021 and September 2021 were prospectively enrolled. The patient’s Glasgow Coma Scale (GCS) score on admission and at discharge and length of stay in hospital were recorded. ICP monitoring data were monitored continuously. The primary endpoint was 6-month Glasgow Outcome Scale-Extended (GOSE) score. Patients with ICP spindle waves were assigned to the spindle wave group and those without were assigned to the control group. The correlation between the spindle wave and 6-month GOSE was analyzed. Meanwhile, the mean ICP and two ICP waveform-derived indices, ICP pulse amplitude (AMP) and correlation coefficient between AMP and ICP (RAP) were comparatively analyzed.

Results: There were no statistically significant differences between groups in terms of age (p = 0.89), gender composition (p = 0.62), and GCS score on admission (p = 0.73). Patients with spindle waves tended to have a higher GCS score at discharge (12.75 vs. 10.90, p = 0.01), a higher increment in GCS score during hospitalization (ΔGCS, the difference between discharge GCS score and admission GCS score) (4.95 vs. 2.80, p = 0.01), and a better 6-month GOSE score (4.90 vs. 3.68, p = 0.04) compared with the control group. And the total duration of the spindle wave was positively correlated with 6-month GOSE (r = 0.62, p = 0.004). Furthermore, the parameters evaluated during spindle waves, including mean ICP, AMP, and RAP, demonstrated significant decreases compared with the parameters before the occurrence of the spindle wave (all p < 0.025).

Conclusion: The ICP spindle wave was associated with a better prognosis in TBI patients. Physiological parameters such as ICP, AMP, and RAP were significantly improved when spindle waves occurred, which may explain the enhancement of clinical outcomes. Further studies are needed to investigate the pathophysiological mechanisms behind this wave.
Bacterial composition of a competitive exclusion product and its correlation with product efficacy at reducing Salmonella in poultry
Authors: Lee Margie D. , Pedroso Adriana A. , Maurer John J.
Published: January 2023

The mature intestinal microbiome is a formidable barrier to pathogen colonization. Day-old chicks seeded with cecal contents of adult hens are resistant to colonization with Salmonella, the basis of competitive exclusion. Competitive exclusion products can include individual microbes but are commonly undefined intestinal communities taken from adult animals and in commercial production is amplified in fermentator and sold commercially in freeze dried lots. While superior to single and multiple species probiotics, reducing Salmonella colonization by multiple logs, undefined products have limited acceptance because of their uncharacterized status. In this study, the bacterial composition of the master stock, preproduction seed stocks and commercial lots of a poultry competitive exclusion product, was defined by 16S rRNA sequence analysis, targeting the 16S rRNA variable region (V1-V3). The samples contained a diversity of genera (22–52 distinct genera) however, the commercial lots displayed less diversity compared to the seeds and the master stock. Community composition varied between seeds and the master stock and was not a good predictor of potency, in terms of log10 reduction in Salmonella abundance. While there was significant correlation in composition between seeds and their commercial lots, this too was a not a good predictor of potency. There was linear correlation between unclassified Actinobacteria, Peptococcus, and unclassified Erysipelotrichaceae, and Salmonella abundance (r2 > .75) for commercial seeds. However, upon review of the literature, these three genera were not consistently observed across studies or between trials that examined the correlation between intestinal community composition and Salmonella prevalence or abundance.
Effects of spinetoram and glyphosate on physiological biomarkers and gut microbes in Bombus terrestris
Authors: Tang Qi-He , Li Wan-Li , Wang Jie-Ping , Li Xi-Jie , Li Dan , Cao Zhe , Huang Qi , Li Jia-Li , Zhang Jun , Wang Zheng-Wei , Guo Jun , Li Ji-Lian
Published: January 2023

The sublethal effects of pesticide poisoning will have significant negative impacts on the foraging and learning of bees and bumblebees, so it has received widespread attention. However, little is known about the physiological effects of sublethal spinetoram and glyphosate exposure on bumblebees. We continuously exposed Bombus terrestris to sublethal (2.5 mg/L) spinetoram or glyphosate under controlled conditions for 10 days. The superoxide dismutase, glutathione-S-transferase, carboxylesterase, prophenoloxidase, α-amylase and protease activities, and changes in gut microbes were measured to understand the effects of sublethal pesticide exposure on the physiology and gut microbes of bumblebees. Sublethal pesticide exposure to significantly increased superoxide dismutase activity and significantly decreased gut α-amylase activity in bumblebees but had no significant effect on glutathione-S-transferase, carboxylesterase or gut protease activities. In addition, glyphosate increased the activity of prophenoloxidase. Interestingly, we observed that neither of the two pesticides had a significant effect on dominant gut bacteria, but glyphosate significantly altered the structure of the dominant gut fungal community, and reduced the relative abundance of Zygosaccharomyces associated with fat accumulation. These results suggest that sublethal spinetoram and glyphosate do not significantly affect the detoxification system of bumblebees, but may affect bumblebee health by inhibiting energy acquisition. Our results provide information on the sublethal effects of exposure to low concentrations of glyphosate and spinetoram on bumblebees in terms of physiology and gut microbes.
Lipidation of small GTPase Cdc42 as regulator of its physiological and pathophysiological functions
Authors: Wirth Alexander , Ponimaskin Evgeni
Published: January 2023

The protein cell division cycle 42 (Cdc42) is a small GTPase of the Rho family regulating a plethora of physiological functions in a tissue, cell and subcellular-specific manner via participating in multiple signaling pathways. Since the corresponding signaling hubs are mainly organized along the cellular membranes, cytosolic proteins like Cdc42 need to be properly targeted and held at the membrane. Here, lipid modifications come into play: Cdc42 can be associated with membranes by different lipid anchors including prenylation (Cdc42-prenyl) and palmitoylation (Cdc42-palm). While Cdc42-prenyl is ubiquitously expressed, Cdc42-palm splicing variant in mainly expressed in the brain. Mechanisms underlying Cdc42 lipidation as well as its regulation are the main topic of this review. Furthermore, we will discuss the functional importance of Cdc42 lipid modifications with the focus on the role of different lipids in regulating defined Cdc42 functions. Finally, we will provide an overview of the possible implementation of Cdc42 lipidation in pathological conditions and different diseases.