bluuebunny/crossref_metadata_2025 huggingface dataset:
Paraventricular oxytocin neurons impact energy intake and expenditure: projections to the bed nucleus of the stria terminalis reduce sucrose consumption
Authors: Worth Amy A. , Feetham Claire H. , Morrissey Nicole A. , Luckman Simon M.
Published: September 2024

Background

The part played by oxytocin and oxytocin neurons in the regulation of food intake is controversial. There is much pharmacological data to support a role for oxytocin notably in regulating sugar consumption, however, several recent experiments have questioned the importance of oxytocin neurons themselves.

Methods

Here we use a combination of histological and chemogenetic techniques to investigate the selective activation or inhibition of oxytocin neurons in the hypothalamic paraventricular nucleus (OxtPVH). We then identify a pathway from OxtPVH neurons to the bed nucleus of the stria terminalis using the cell-selective expression of channel rhodopsin.

Results

OxtPVH neurons increase their expression of cFos after both physiological (fast-induced re-feeding or oral lipid) and pharmacological (systemic administration of cholecystokinin or lithium chloride) anorectic signals. Chemogenetic activation of OxtPVH neurons is sufficient to decrease free-feeding in OxtCre:hM3Dq mice, while inhibition in OxtCre:hM4Di mice attenuates the response to administration of cholecystokinin. Activation of OxtPVH neurons also increases energy expenditure and core-body temperature, without a significant effect on locomotor activity. Finally, the selective, optogenetic stimulation of a pathway from OxtPVH neurons to the bed nucleus of the stria terminalis reduces the consumption of sucrose.

Conclusion

Our results support a role for oxytocin neurons in the regulation of whole-body metabolism, including a modulatory action on food intake and energy expenditure. Furthermore, we demonstrate that the pathway from OxtPVH neurons to the bed nucleus of the stria terminalis can regulate sugar consumption.
Different intensities of aerobic training for patients with type 2 diabetes mellitus and knee osteoarthritis: a randomized controlled trial
Authors: Su Chi , Huang Lihua , Tu Shaochen , Lu Shengdi
Published: September 2024

Objective

The purpose of this study was to compare different intensities of aerobic exercise for patients with knee osteoarthritis (KOA) and type 2 diabetes mellitus (T2DM) in terms of glycemic control, pain relief, and functional outcomes.

Methods

A prospective randomized open-label parallel multicenter clinical trial conducted at two hospitals in Shanghai and Sichuan that included 228 patients with type 2 diabetes mellitus (T2DM) and knee osteoarthritis (KOA). Enrollment occurred between January 2021 and February 2023, and follow-up was completed in September 2023. Participants were randomized to threshold training/high-intensive stationary cycling training (n=76), intensive endurance/moderate-intensive stationary cycling training (n=77), and regular rehabilitation programs (n=75). The primary outcome at the 6-month follow-up was the HbA1c level. Key secondary outcomes included the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscale of pain and quality of life.

Results

Of 228 patients, 212 (93%) completed the trial. The mean adjusted (sex, baseline BMI, and baseline outcome measures) HbA1c level at the 6-month follow-up decreased significantly in the high-intensive training group compared with other groups (high-intensity group vs. control group; difference, 0.51%, 95% confidence interval, 0.05% to 1.15%). Mean KOOS subscales of pain and quality of life were statistically significantly different between the control group and moderate-intensity or high-intensity groups, but no statistical differences were noted between the different intensities of aerobic exercise. Patients in all groups achieved a greater reduction in BMI but no significant differences were observed between groups.

Conclusion

In KOA and T2DM patients, high-intensity stationary cycling can significantly improve glycemic control compared with moderate-intensity and regular rehabilitation programs. However, high-intensity stationary cycling does not exert a superior effect on pain relief and functional improvement for KOA compared with moderate-intensity and regular rehabilitation programs.
Effects of dietary supplementation with medicinal plant mixtures and immunostimulants on the immune response, antioxidant capacity, and hepatopancreatic health of Chinese mitten crab (Eriocheir sinensis)
Authors: Wang Anran , Xu Jie , Zhang Xin , Liu Xuran , Li Mengge , Dong Xiaojing , Miao Shuyan
Published: September 2024

Introduction

This study aimed to evaluate the efficiency of tea polyphenols (TP) and medicinal plant mixtures (Astragalus membranaceus + Lonicera japonica, Rheum officinale Bail + Scutellaria baicalensis + Platycladus orientalis) combined with astaxanthin (AST), benzoic acid (BA), and yeast complex on the health status of Eriocheir sinensis.

Method

A total of 630 crabs (male crabs: 41.51 ± 1.63 g; female crabs: 47.27 ± 0.79 g) were randomly distributed into seven groups with three replicates (male: female, 1:1). These crabs were fed as follows for 8 weeks: basal diet (M1), M2 (M1 + 100 mg/kg TP), M3 (M1 + 2.0 g/kg A. membranaceus + 20 g/kg L. japonica), M4 (M1 + 2.5 g/kg R. officinale Bail + 1.5 g/kg S. baicalensis + 1.0 g/kg P. orientalis), and M5, M6, M7 (M2, M3 and M4 with 600 mg/kg AST +1.0 g/kg BA + 20 mg/kg yeast complex added, respectively).

Results and discussion

The results showed that the activities of acid phosphatase (ACP), alkaline phosphatase (AKP), and lysosome (LZM) in the hemolymph were significantly increased in M5, M6, and M7 (P < 0.05), and the highest phagocytosis index (PI) and LZM activity were observed in M7 of female crabs. Moreover, the antioxidant indicators superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT) of hepatopancreas were also significantly improved in M5, M6, and M7 (P < 0.05), while the malondialdehyde (MDA) contents showed an opposite trend. Furthermore, a morphological examination also showed the improved histological structure of hepatopancreas in M7, especially as seen in the clear lumens, no vacuolation, and integrity of the basal membrane of the hepatopancreatic tubule. Taken together, these results suggested that 2.5 g/kg R. officinale Bail, 1.5 g/kg S. baicalensis, and 1.0 g/kg P. orientalis in combination with 600 mg/kg AST, 1.0 g/kg BA, and 20 mg/kg yeast complex could improve the non-specific immunity, antioxidant capacity, and hepatopancreatic health of E. sinensis.
Case report: Granulocyte-macrophage colony-stimulating factor sargramostim did not rescue the neutrophil phenotype in two patients with JAGN1-mutant severe congenital neutropenia
Authors: Farmand Susan , Aydin Susanne Eva , Wustrau Katharina , Böhm Svea , Ayuk Francis , Escherich Gabriele , Skokowa Julia , Müller Ingo , Lehmberg Kai
Published: September 2024

Background

Homozygous or compound heterozygous mutations in JAGN1 cause severe congenital neutropenia. JAGN1-mutant patients present with severe early-onset bacterial infections and most have been described as low-responders to recombinant granulocyte colony-stimulating factor (G-CSF) therapy. In a murine, hematopoietic JAGN1 knockout model, which displays susceptibility to Candida albicans infection in the absence of neutropenia, treatment with granulocyte-macrophage-CSF (GM-CSF) was able to restore the functional defect of neutrophils.

Patients

We present two unrelated patients with biallelic JAGN1 mutations, who were both treated with subcutaneous GM-CSF (sargramostim) after treatment failure to G-CSF. The first patient was an 18-year-old pregnant woman who received GM-CSF at 12 weeks of gestation up to a dose of 10 µg/kg/d for 7 days. The second patient was a 5-month-old girl who received GM-CSF for a total of 9 days at a dose of up to 20 µg/kg/d. GM-CSF did not increase neutrophil counts in our patients. Treatment was stopped when neutrophil numbers declined further, no beneficial effect was noticed, and patients presented with infections. No adverse effects were observed in either patient and the fetus. Both patients ultimately underwent successful hematopoietic stem cell transplantation.

Discussion

Both patients showed a high recurrence rate of severe infections on G-CSF treatment. GM-CSF therapy did not ameliorate the clinical phenotype, in contrast to the improvement of neutrophil function observed in the JAGN1 mouse model. No major additional extra-hematopoietic manifestations were evident in our patients.

Conclusion

In two unrelated patients, GM-CSF did not have any beneficial effect on neutrophil counts. Patients with JAGN1-mutant SCN with reduced G-CSF responsiveness and elevated infection rate should be evaluated early for stem cell transplantation.
The causal relationship between immune cells and diabetic retinopathy: a Mendelian randomization study
Authors: Ye Yunyan , Dai Lei , Gu Hong , Yang Lan , Xu Zhangxing , Li Zhiguo
Published: September 2024

Purpose

This article explored the causal relationship between immune cells and diabetic retinopathy (DR) using single nucleotide polymorphisms (SNPs) as an instrumental variable and Mendelian randomization (MR).

Methods

Statistical data were collected from a publicly available genome-wide association study (GWAS), and SNPs that were significantly associated with immune cells were used as instrumental variables (IVs). Inverse variance weighted (IVW) and MR−Egger regression were used for MR analysis. A sensitivity analysis was used to test the heterogeneity, horizontal pleiotropy, and stability of the results.

Results

We investigated the causal relationship between 731 immune cells and DR risk. All the GWAS data were obtained from European populations and from men and women. The IVW analysis revealed that HLA DR on CD14+ CD16- monocytes, HLA DR on CD14+ monocytes, HLA DR on CD33-HLA DR+, HLA DR on CD33+ HLA DR+ CD14- on CD33+ HLA DR+ CD14dim, and HLA DR on myeloid dendritic cells may increase the risk of DR (P<0.05). HLA DR to CD14-CD16- cells, the monocytic myeloid-derived suppressor cell absolute count, the SSC-A count of CD4+ T cells, and terminally differentiated CD4+ T cells may be protective factors against DR (P<0.05). The sensitivity analysis indicated no heterogeneity or pleiotropy among the selected SNPs. Furthermore, gene annotation of the SNPs revealed significant associations with 10 genes related to the risk of developing PDR and potential connections with 12 other genes related to PDR.

Conclusion

Monocytes and T cells may serve as new biomarkers or therapeutic targets, leading to the development of new treatment options for managing DR.
Proliferation capability of natural killer cells upon cytokines stimulation correlated negatively with serum lactate dehydrogenase level in coronary artery disease patients
Authors: Guo Xuemin , Xiao Ting , Lin Li , Gao Qianqian , Lai Bifa , Liu Xianhui , Zhong Zhixiong
Published: September 2024

Background

Natural killer (NK) cells are proposed to participate in coronary artery disease (CAD) development. However, little is known about how CAD patients’ NK cells respond to different stimulatory factors in terms of proliferation capability.

Methods and results

Twenty-nine CAD patients’ peripheral blood NK cells were isolated and individually treated with IL-2, IL-12, IL-15, IL-18, IL-21, cortisone acetate, hydrocortisone, or ascorbic acid for 36 hours, followed by cell cycle analysis using flow cytometry. The ratio of S and G2/M phase cell number to total cell number was defined as a proliferation index (PrI) and used for proliferative capability indication. The results showed that these eight factors resulted in different life cycle changes in the 29 NK cell samples. Remarkably, 28 out of 29 NK cell samples showed an obvious increase in PrI upon ascorbic acid treatment. The serum lactate dehydrogenase (LDH) level of the 29 CAD patients was measured. The results showed a negative correlation between serum LDH level and the CAD patients’ NK cell PrI upon stimulation of interleukins, but not the non-interleukin stimulators. Consistently, a retrospective analysis of 46 CAD patients and 32 healthy donors showed that the circulating NK cell number negatively correlated with the serum LDH level in CAD patients. Unexpectedly, addition of LDH to NK cells significantly enhanced the production of IFN-γ, IL-10 and TNF-α, suggesting a strong regulatory role on NK cell’s function.

Conclusion

Ascorbic acid could promote the proliferation of the CAD patients’ NK cells; LDH serum level may function as an indicator for NK cell proliferation capability and an immune-regulatory factor.
Booster vaccination using bivalent DS-5670a/b is safe and immunogenic against SARS-CoV-2 variants in children aged 5–11 years: a phase 2/3, randomized, active-controlled study
Authors: Suzuki Rino , Suda Miharu , Ishida Katsuyasu , Furihata Kei , Ota Aisaku , Takahashi Kaori , Sakakibara Sachiko , Nakayama Tetsuo , Takeshita Fumihiko
Published: September 2024

Background

DS-5670 is a messenger ribonucleic acid (mRNA) vaccine platform targeting the receptor-binding domain (RBD) of the spike protein derived from severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Booster vaccination against coronavirus disease 2019 (COVID-19) with monovalent DS-5670a (incorporating mRNA encoding the RBD from the original SARS-CoV-2 strain) or bivalent DS-5670a/b (original and omicron BA.4-5 RBD antigens) is effective and safe in adults. Data from a phase 2/3 active-controlled, non-inferiority, pediatric study evaluating a third booster dose of DS-5670a/b are reported here.

Methods

Children aged 5–11 years who had completed the two-dose primary vaccination series with monovalent BNT162b2 (original strain) at least 3 months prior to enrolment were randomly assigned to receive DS-5670a/b (20 µg of mRNA) or bivalent BNT1 62b2 (original/omicron BA.4-5; 10 µg of mRNA) on Day 1. The primary efficacy endpoint was blood neutralization geometric mean titer (GMT) against SARS-CoV-2 (omicron variant BA.5.2.1) and immune response rate (≥ 4-fold increase in post-vaccination circulating anti-SARS-CoV-2 neutralizing activity) on Day 29.

Results

Among evaluable participants (DS-5670a/b, n = 74; bivalent BNT162b2, n = 75), the adjusted GMT ratio of DS-5670a/b to bivalent BNT162b2 on Day 29 was 1.636 (95% CI, 1.221, 2.190). Immune response rates were ≥ 89% with both study vaccines; adjusted difference 2.6% (95% CI, –7.8, 13.8). The prespecified non-inferiority margins were exceeded, and the study met the primary endpoint. DS-5670a/b also demonstrated broad neutralization activity across recent omicron sublineages and no cases of COVID-19 between Days 8–29 post-administration were reported. There were no novel safety concerns in the pediatric population at data cut-off.

Conclusions

Bivalent DS-5670a/b was non-inferior to bivalent BNT162b2 in terms of immunogenicity, and had a manageable safety profile, when administered as a heterologous booster in children aged 5–11 years.

Clinical trial registration

https://jrct.niph.go.jp/, identifier jRCT2031220665
Strengthening lupus education and coordinated care in developing countries
Authors: Navarra Sandra V.
Published: September 2024

SLE is a chronic autoimmune disease with a wide range of manifestations and potential to affect several organ systems. Complications arise from both disease and medications especially glucocorticoids, significantly contributing to overall morbidity and mortality. SLE predominantly affects patients during their prime productive years resulting in substantial economic burden on the patient, caregivers and society due to direct, indirect and intangible costs. In developing countries with limited resources, efficient healthcare delivery for most lupus patients remains elusive. This is magnified by the increasing shortage of rheumatologists and lupus specialists. Physician education starting in medical school as well as practical referral pathways and physician networking in clinical practice ensure continuity of and coordinated care for every lupus patient. Likewise, education of allied health professionals, patient empowerment and self-help programs help improve overall outcomes in SLE.
Structural variability of protist assemblages in surface sediments across Italian Mediterranean marine subregions
Authors: Marinchel Nadia , Casabianca Silvia , Marchesini Alexis , Vernesi Cristiano , Scardi Michele , Penna Antonella
Published: September 2024

Marine sediments host heterogeneous protist communities consisting of both living benthic microorganisms and planktonic resting stages. Despite their key functions in marine ecosystem processes and biogeochemical cycles, their structure and dynamics are largely unknown. In the present study, with a spatially intensive sampling design we investigated benthic protist diversity and function of surface sediment samples from three subregions of the Mediterranean Sea, through an environmental DNA metabarcoding approach targeting the 18S V4 region of rRNA gene. Protists were characterized at the taxonomic level and trophic function, both in terms of alpha diversity and community composition, testing for potential differences among marine subregions and bathymetric groups. Overall, Alveolata and Stramenopiles were the two divisions that dominated the communities. These dominant groups exhibited significant differences among the three Mediterranean subregions in the alpha diversity estimates based on the detected ASVs, for all computed indices (ASV richness, Shannon and Simpson indices). Protist communities were also found to be significantly different in terms of composition at the order rank in the three subregions p-value < 0.01). These differences were mainly driven by Anoecales, Peridiniales, Borokales, Paraliales and Gonyaulacales, which together contributed almost 80% of the average dissimilarity. Anoecales was the dominant order in the Ionian – Central Mediterranean and Adriatic Sea, but with considerably different relative abundances (52% and 36%, respectively), while Borokales was the dominant order in the Western Mediterranean Sea (33%). Similarly, significant differences among the three marine subregions were also highlighted when protist assemblages were examined in terms of trophic function, both in terms of alpha diversity (calculated on the ASVs for each trophic group) and community composition p-value < 0.01. In particular, the Adriatic Sea stood out for having the highest relative abundance of autotrophic/mixotrophic components in the surface sediments analyzed. Conversely, no significant differences in protist assemblages were found among depth groups. This study provided new insights into the taxonomic and trophic composition of benthic protist communities found in Mediterranean surface sediments, revealing geographical differences among regional seas. The results were discussed in relation to the Mediterranean environmental features that could generate the differences among benthic protist communities.
Detrital zircons record the provenance and source-to-sink process in the northwestern margin of the South China Sea
Authors: Cui Heqi , Wang Ce , Su Ming , Lei Yaping , Zeng Letian , Jia Junmin
Published: September 2024

The northwestern continental margin of the South China Sea, extending from the broad shelf and canyon-growth slope across the Xisha Trough, represents a relic crustal rift that eventually connects to the abyssal plain. However, the provenance and source-to-sink process of sediments in this special topography remains unclear. In this study, we present the detrital zircon U-Pb geochronology of surface sediments from the northwestern margin of the South China Sea to identify the sediment provenance, track the transport pathway, and understand the source-to-sink process in this margin. The results showed that detrital zircons exhibit a wide range of U-Pb ages from 3,062.9 to 41.5 Ma and are characterized by peaks centered on 140–154 Ma, 240–258 Ma, 425–452 Ma, and 738–991 Ma. Statistical analysis indicated that the clastic sediments on the shelf closely resemble those sourced from the Pearl River system. Conversely, sediments on the slope and abyssal plain demonstrated characteristics indicative of multiple sources, primarily originating from the Pearl River, with a minor contribution from the Red River. Further quantitative study revealed a progressive increase (from 8.2% to 43.2%) in the prevalence of Red River-derived sediments with ascending water depth on the shelf and slope, whereas sediment influx in the deepest sector remains predominantly sourced from the Pearl River. This study emphasizes the controls of topography and currents in modulating the transportation of coarse-grained and fine-grained sediments within the source-to-sink system and provides a favorable solution for reconstructing the sedimentary process in continental margins.
Dynamic properties of CO2-cured foam concrete at different loading rates: Effect of the foam admixtures and addition of polypropylene fiber
Authors: Liu Yunlin , Huo Shangwei , Fu Jiali , Shi Tingbo , Guo Dong
Published: September 2024

This paper investigated the dynamic mechanical properties of CO2-cured foam concrete under varying conditions, focusing on the effects of foam admixture and fiber reinforcement. The study tends to enrich the knowledge regarding the performance of CO2-cured foam concrete under different loading rates, especially in relation to density and matrix strength. The foam admixture of the specimens ranges from 26% to 55%, achieving density from 600 kg/m3 to 1,000 kg/m3. The specimens were loaded at strain rates from 80 s-1 to 398 s-1. Experimental results revealed the dynamic elastic modulus, dynamic compressive strength, and Dynamic Increase Factor (DIF) showed a strong correlation with the foam admixture and density. In addition, the incorporation of polypropylene (PP) fibers effectively improved the mechanical behavior of the foam concrete, achieving up to a 17% increase in dynamic compressive strength. This comprehensive analysis highlights the critical role of foam admixture and fiber reinforcement in determining the dynamic properties of CO2-cured foam concrete and provides valuable insights for optimizing the dynamic performance of foam concrete in various construction applications.
Recent advancements toward the incremsent of drug solubility using environmentally-friendly supercritical CO2: a machine learning perspective
Authors: Alamoudi Jawaher Abdullah
Published: September 2024

Inadequate bioavailability of therapeutic drugs, which is often the consequence of their unacceptable solubility and dissolution rates, is an indisputable operational challenge of pharmaceutical companies due to its detrimental effect on the therapeutic efficacy. Over the recent decades, application of supercritical fluids (SCFs) (mainly SCCO2) has attracted the attentions of many scientists as promising alternative of toxic and environmentally-hazardous organic solvents due to possessing positive advantages like low flammability, availability, high performance, eco-friendliness and safety/simplicity of operation. Nowadays, application of different machine learning (ML) as a versatile, robust and accurate approach for the prediction of different momentous parameters like solubility and bioavailability has been of great attentions due to the non-affordability and time-wasting nature of experimental investigations. The prominent goal of this article is to review the role of different ML-based tools for the prediction of solubility/bioavailability of drugs using SCCO2. Moreover, the importance of solubility factor in the pharmaceutical industry and different possible techniques for increasing the amount of this parameter in poorly-soluble drugs are comprehensively discussed. At the end, the efficiency of SCCO2 for improving the manufacturing process of drug nanocrystals is aimed to be discussed.
Impact of multiple infections on risk of incident dementia according to subjective cognitive decline status: a nationwide population-based cohort study
Authors: Lee Jung-Won , Kim Mina , Kim Hoseob , Kim Sunghwan , Um Yoo Hyun , Wang Sheng-Min , Lim Hyun Kook , Lee Chang Uk , Kang Dong Woo
Published: September 2024

Background

The interrelation between infections, subjective cognitive decline (SCD), and dementia development is recognized, but not fully understood. This study explored the combined effect of specific infections and SCD on the risk of dementia.

Objectives

To assess the influence of Helicobacter pylori, herpes simplex virus, varicella-zoster virus, and human papillomavirus on dementia risk in individuals with varying cognitive statuses, especially focusing on those with and without SCD.

Methods

A cohort of 1,100,540 participants aged 66 years from the Korean National Health Insurance Service was divided into cognitively preserved (CP, n = 825,405) and SCD (n = 275,135) groups. This study analyzed the effects of single, dual, and triple infections on the risk of overall dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) using incidence rates and hazard ratios.

Results

The SCD group consistently showed a doubled risk of dementia, particularly AD, regardless of the number of infections. In the initial data, both the presence and number of infections, especially in the CP group, were associated with an increased dementia incidence and risk; however, this correlation disappeared after adjusting for covariates, hinting at a possible protective effect.

Conclusion

Our findings emphasize that, while SCD is a steadfast risk factor for dementia, the role of infections is layered, subject to various influences, and requires more comprehensive exploration to fully understand their impact on dementia development.
A systematic review of steroid use in peripheral nerve pathologies and treatment
Authors: Couch Brandon , Hayward Dan , Baum Gracie , Sakthiyendran Naveen Arunachalam , Harder Justin , Hernandez Evan J. , MacKay Brendan
Published: September 2024

Background

The use of corticosteroids has become a part of the standard of care in various pathologies but their use in peripheral nerve injury treatment is limited. Given corticosteroids’ anti-inflammatory properties and their regulatory role in neuronal protein production and myelination, corticosteroids could serve as an adjunct therapy for peripheral nerve injuries. This review aims to systematically investigate the current use of corticosteroid treatment in peripheral nerve pathologies.

Methods

The systematic search was performed on PubMed, MEDLINE, EMBASE, Scopus, Cochrane, and Web of Science using keywords such as “corticosteroid treatment,” “peripheral nerve damage,” “peripheral neuropathy,” and “complications.” The PRISMA guidelines were used to conduct the systematic review and all articles were reviewed by the corresponding author. After the initial search, individual study titles and abstracts were further screened and categorized using an inclusion and exclusion criteria followed by a final full-text review.

Results

Out of the total 27,922 identified records, 203 studies were included based on the selection criteria. These studies focused on the use and efficacy of steroids across a spectrum of compression and non-compression peripheral neuropathies such as cubital tunnel syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. Various studies noted the promising role of steroids in offering pain relief, nerve block, and nerve regeneration effects. Additionally, safety considerations and potential complications regarding steroid use in peripheral nerve injuries were analyzed.

Conclusion

While there is currently limited clinical utilization of corticosteroids in peripheral nerve pathologies, the anti-inflammatory and regenerative effects that steroids provide may be a beneficial tool in managing various peripheral neuropathies and their associated pain. Additional clinical trials and investigation into the mechanism of action could improve the reputation of steroid use as peripheral nerve injury treatment.
Sex steroid hormone residues in milk and their potential risks for breast and prostate cancer
Authors: Gao Pengyue , Li Chengyi , Gong Quan , Liu Lian , Qin Rui , Liu Jiao
Published: September 2024

Milk was a source of important nutrients for humans and was especially important for children and adolescents. The modern dairy animal production pattern had contributed to residual sex steroid hormones in milk. When this milk was consumed by humans, these hormones entered the body leading to hormonal disruptions and potentially increasing the risk of various types of cancers. This article reviewed the presence of residual sex steroid hormones in milk, their potential risks on human health, and their possible association with the incidence of breast and prostate cancer. The potential linkage between dairy consumption and these cancers were described in detail. The hormones present in dairy products could affect the development and progression of these types of cancer. Sex steroid hormones could interact with different signaling pathways, influencing carcinogenic cascades that could eventually lead to tumorigenesis. Given these potential health risks, the article suggested appropriate consumption of dairy products. This included being mindful not just of the amount of dairy consumed, but also the types of dairy products selected. More scientific exploration was needed, but this review provided valuable insights for health-conscious consumers and contributed to the ongoing discussion on dietary guidelines and human health.
Causal relationship between dietary intake and IgA nephropathy: a Mendelian randomization study
Authors: Li Yaping , Wan Shengli , Liu Jing , Huang Yilan , Jiang Longyang
Published: September 2024

Objective

Previous studies have reported that dietary intake is associated with immunoglobulin A nephropathy (IgAN). However, the causal relationship remains unknown. Based on publicly available genome-wide association study (GWAS) data, we conducted a two-sample Mendelian randomization (MR) analysis to assess the causal association between 26 dietary exposures and IgAN.

Methods

Five methods, including inverse variance weighting (IVW), MR–Egger regression, weighted median, simple mode, and weighted mode, were applied in the MR analysis. To identify the presence of horizontal pleiotropy, we used the MR-Egger intercept test and MR pleiotropy residual sum and outlier (MR-PRESSO) global test. Cochran’s Q statistics were used to assess instrument heterogeneity. We conducted sensitivity analysis using the leave-one-out method.

Results

Finally, the results indicated alcohol intake frequency (odds ratio [OR] (95% confidence interval [CI]) = 1.267 (1.100–1.460), p = 0.0010295) was a risk factor of IgAN, while cheese intake (OR (95% CI) = 0.626 (0.492–0.798), p = 0.0001559), cereal intake (OR (95% CI) = 0.652 (0.439–0.967), p = 0.0334126), and sushi intake (OR (95% CI) = 0.145 (0.021–0.997), p = 0.0497) were protective factors of IgAN. No causal relationship was found between IgAN and the rest of the dietary exposures.

Conclusion

Our study provided genetic evidence that alcohol intake frequency was associated with an increased risk of IgAN, while cheese, cereal, and sushi intake were associated with a decreased risk of IgAN. Further investigation is required to confirm these results.
Prognostic nomogram of overall survival for radiation therapy in hepatocellular carcinoma: a population study based on the SEER database and an external cohort
Authors: Chen Lijun , Wu Qiaoyuan , Fu Jia , Jiang Mengjie , Qiu Jialin , Tao Jiaomei , Lin Litong , Chen Shenshen , Wu Yi , Yang Zhengqiang , Li Jianxu , Liang Shixiong
Published: September 2024

Purpose

Radiotherapy (RT) plays an important role in the treatment of hepatocellular carcinoma (HCC). To screen patients who benefit most from RT, a nomogram for survival prediction of RT based on a large sample of patients with HCC was created and validated.

Methods

A total of 2,252 cases collected from the Surveillance, Epidemiology, and End Results (SEER) database were separated into a training or an internal validation cohort in a 7:3 ratio (n = 1,565:650). An external validation cohort of cases from our institute was obtained (n = 403). LASSO regression and Cox analyses were adopted to develop a nomogram for survival prediction. The decision curve analysis (DCA), calibration curve, and time-dependent receiver operating characteristic curves (TROCs) demonstrated the reliability of the predictive model.

Results

For patients with HCC who received RT, the analyses revealed that the independent survival prediction factors were T stage {T2 vs. T1, hazard ratio (HR) =1.452 [95% CI, 1.195–1.765], p < 0.001; T3 vs. T1, HR = 1.469 [95% CI, 1.168–1.846], p < 0.001; T4 vs. T1, HR = 1.291 [95% CI, 0.951–1.754], p = 0.101}, N stage (HR = 1.555 [95% CI, 1.338–1.805], p < 0.001), M stage (HR = 3.007 [95% CI, 2.645–3.418], p < 0.001), max tumor size (>2 and ≤5 vs. ≤2 cm, HR = 1.273 [95% CI, 0.992–1.633], p = 0.057; >5 and ≤10 vs. ≤2 cm, HR = 1.625 [95% CI, 1.246–2.118], p < 0.001; >10 vs. ≤2 cm, HR = 1.784 [95% CI, 1.335–2.385], p < 0.001), major vascular invasion (MVI) (HR = 1.454 [95% CI, 1.028–2.057], p = 0.034), alpha fetoprotein (AFP) (HR = 1.573 [95% CI, 1.315–1.882], p < 0.001), and chemotherapy (HR = 0.511 [95% CI, 0.454–0.576], p < 0.001). A nomogram constructed with these prognostic factors demonstrated outstanding predictive accuracy. The area under the curve (AUC) in the training cohort for predicting overall survival (OS) at 6, 12, 18, and 24 months was 0.824 (95% CI, 0.803–0.846), 0.824 (95% CI, 0.802–0.845), 0.816 (95% CI, 0.792–0.840), and 0.820 (95% CI, 0.794–0.846), respectively. The AUCs were similar in the other two cohorts. The DCA and calibration curve demonstrated the reliability of the predictive model.

Conclusion

For patients who have been treated with RT, a nomogram constructed with T stage, N stage, M stage, tumor size, MVI, AFP, and chemotherapy has good survival prediction ability.
Role of FGF21 in mediating the effect of phosphatidylcholine on GBM
Authors: Wang Peng , Zhang Xin , Xiao Boan , Ouyang Jiecai , Zhang Jingjing , Peng Xiaobin
Published: September 2024

Objective

The causal relationship and mechanisms between lipids and glioblastoma (GBM) remain unclear. This study aims to investigate the independent causal relationship between liposomal phosphatidylcholine 16:0_22:6 (PC16) and GBM, and to identify the potential mediating role of the inflammatory factor-fibroblast growth factor 21(FGF21).

Methods

Utilizing summary statistics from genome-wide association studies (GWAS) of lipids (179 types in 7174 Finnish individuals), GBM (243 cases and 287137 controls), and inflammatory factors (91 types in 14824 European individuals), a two-sample Mendelian Randomization (MR) approach was employed to establish the causal link between liposomal PC16 and GBM. Additionally, a two-step MR method was used to quantify the proportion of the causal effect of PC16 on GBM that is mediated by the inflammatory factor FGF21.

Results

MR analyses revealed a strong causal relationship between PC16 and GBM (OR=1.72, 95% CI: 1.11-2.68, P=0.016), but no reverse causality was observed from GBM to PC16 (OR=1.01, 95% CI: 0.99-1.02, P=0.38). Mediation analysis showed a strong causal relationship between PC16 and the FGF21 (OR = 0.94, 95% CI: 0.89-0.99, P=0.018) as well as between FGF21 and GBM (OR = 0.42, 95% CI: 0.25-0.71, P=0.001), with the mediation effect accounting for 9.78% of the total effect. This suggests that the causal relationship between PC16 and GBM is likely mediated by the intermediary factor FGF21. No evidence of pleiotropy was found in the sensitivity analysis of these positive results.

Conclusion

In summary, the findings of this study suggest that liposomal PC16 may increase the risk of GBM occurrence, and FGF21 may play a significant mediating role in this causal relationship.
Inhibition of ADAM17 increases the cytotoxic effect of cisplatin in cervical spheroids and organoids
Authors: Holthaus David , Rogmans Christoph , Gursinski Ina , Quevedo-Olmos Alvaro , Ehsani Marzieh , Mangler Mandy , Flörkemeier Inken , Weimer Jörg P. , Meyer Thomas F. , Maass Nicolai , Bauerschlag Dirk O. , Hedemann Nina
Published: September 2024

Introduction

Cervical cancer represents one of the main causes of female, cancer-related mortality worldwide. The majority of cancers are caused by human papillomaviruses such as HPV16 and HPV18. As chemotherapeutic resistance to first-line platinum treatment is still a predominant clinical challenge in advanced cervical cancer, novel treatment options including combinatorial therapies are urgently required to overcome chemotherapeutic resistance. Inhibition of A Disintegrin And Metalloproteinase (ADAM)-family members, heavily involved in tumour progression of a vast range of solid tumours, strongly improved response to chemotherapeutic treatment in other tumour entities including ovarian cancer.

Methods

We established two- and three-dimensional models derived from three traditional cervical cancer cell lines and ectocervical cancer-derived organoids. Following characterisation, these models were used to investigate their response to cisplatin treatment in the absence and presence of ADAM inhibitors using viability assays and automated live cell imaging.

Results

The pivotal role of the metalloprotease ADAM17 driving chemotherapy resistance was detectable in all ectocervical cultures irrespective of the model system used, whereas ADAM10 inhibition was predominantly effective only in loosely aggregated spheroids. We showed prominent differences regarding treatment responses between 2D monolayers compared to 3D spheroid and 3D organoid model systems. Particularly, the organoid system, regarded as the closest representation of primary tumours, exhibited reliably the combinatorial effect of ADAM17 inhibition and cisplatin in all three individual donors.

Discussion

As two- and three-dimensional models of the same cell lines differ in their responses to chemotherapy it is essential to validate treatment strategies in more advanced model systems representing the patient situation more realistically. Ectocervical organoids showed reliable results regarding treatment responses closely mimicking the primary tumours and could therefore serve as an important tool for personalized medicine in cervical cancer. These findings strengthen the role of ADAM17 as a potential novel target for combinatorial treatments to overcome chemoresistance in cervical cancer.
Comprehensive analysis of splicing factor SRs-related gene characteristics: predicting osteosarcoma prognosis and immune regulation status
Authors: Long Changhai , Ma Biao , Li Kai , Liu Sijing
Published: September 2024

Objective

To investigate the impact of SRs-related genes on the overall survival and prognosis of osteosarcoma patients through bulk and single-cell RNA-seq transcriptome analysis.

Methods

In this study, we constructed a prognosis model based on serine/arginine-rich splicing factors (SRs) and predicted the survival of osteosarcoma patients. By analyzing single-cell RNA sequencing data and applying AUCell enrichment analysis, we revealed oncogenic pathways of SRs in osteosarcoma immune cells. Additionally, we described the regulatory role of SRSF7 in pan-cancer.

Results

Lasso regression analysis identified 6 key SRs-related genes, and a prognosis prediction model was established. The upregulation of these pathways revealed that SRs promote tumor cell proliferation and survival by regulating related signaling pathways and help tumor cells evade host immune surveillance. Additionally, by grouping single-cell data using AUCell, we found significant differences in T cell expression between high and low-risk groups. The analysis results indicated that the regulatory activity of SRs is closely related to T cell function, particularly in regulating immune responses and promoting immune evasion. Furthermore, SRSF7 regulates cell proliferation and apoptosis.

Conclusion

SRs-related genes play a critical regulatory role in osteosarcoma. T cells are key in regulating immune responses and promoting immune evasion through SRs genes. SRSF7 is a significant gene influencing the occurrence and development of osteosarcoma.
Schistosomiasis endemicity and its role in sexually transmitted infections – a systematic review and meta-analysis
Authors: Asare Kwame Kumi , Afful Philip , Abotsi Godwin Kwami , Adu-Gyamfi Czarina Owusua , Benyem George , Katawa Gnatoulma , Arndts Kathrin , Ritter Manuel
Published: September 2024

Introduction

Schistosomiasis, a tropical parasitic disease, affects 779 million people globally, with 85% of cases in Africa. The interplay between schistosomiasis and other sexually transmitted infections (STIs) can exacerbate health burdens, but most attention has focused on interactions with HIV, neglecting coinfections with other STIs. This systematic review and meta-analysis aims to understand the role Schistosoma infections play in STIs within schistosomiasis-endemic populations.

Methods

The study is a systematic review and meta-analysis investigating the link between Schistosoma infections and STIs in endemic regions. It uses PRISMA guidelines, electronic databases, and Google Scholar to assess prevalence, associations, and heterogeneity, reducing bias using a Meta-Mar statistical tool.

Results

A quantitative synthesis of 33 articles from 1975–2024 involved 22,587 participants from 13 countries, including regions in Africa, France, and China, examining coinfections of schistosomiasis and STIs, including HIV. The pooled estimates showed a significant risk association between schistosomiasis and STIs [RR (95% CI) = 1.18, (1.13–1.24); z/t = 7.55, p<0.0001] using a fixed effect model. Cochran’s Q test (Tau2 = 0.5061, Chi2 = 476.65, df = 32, p<0.01) indicated significant heterogeneity. The Higgins I2 statistic of 93.0% (91.5%–94.7%), H = 3.86 (3.43–4.33), highlighted substantial variance between studies. Subgroup analysis showed West Africa [Weight IV = 1.7%, RR (95% CI) = 1.78 (1.28–2.47), I2 = 59%], East Africa [Weight IV = 10.5%, RR (95% CI) = 0.99 (0.86–1.13), I2 = 54%], and Southern Africa [Weight IV = 82.0%, RR (95% CI) = 1.16 (1.10–1.21), I2 = 97%] contributed significantly to the high heterogeneity in the pooled analysis. Females had a notably higher risk of STIs in the context of schistosomiasis (k = 17, RR: 1.30, 95% CI: 1.23–1.37, Q = 316.78, I2 = 94.9%), compared to males (k = 6, RR: 0.94, 95% CI: 0.77–1.15, Q = 53.44, I2 = 90.6%) and the combined group of females and males (k = 9, RR: 0.95, 95% CI: 0.88–1.02, Q = 16.38, I2 = 50.2%).

Conclusion

The study found a high risk of coinfections between schistosomiasis and STIs, particularly in West and Southern Africa, confirming female genital schistosomiasis as a major risk for STIs.
Unveiling the contribution of tumor-associated macrophages in driving epithelial-mesenchymal transition: a review of mechanisms and therapeutic Strategies
Authors: Zhang Yijia , Ding Xiaofei , Zhang Xue , Li Ye , Xu Rui , Li Hai-Jun , Zuo Daiying , Chen Guang
Published: September 2024

Tumor-associated macrophages (TAMs), fundamental constituents of the tumor microenvironment (TME), significantly influence cancer development, primarily by promoting epithelial-mesenchymal transition (EMT). EMT endows cancer cells with increased motility, invasiveness, and resistance to therapies, marking a pivotal juncture in cancer progression. The review begins with a detailed exposition on the origins of TAMs and their functional heterogeneity, providing a foundational understanding of TAM characteristics. Next, it delves into the specific molecular mechanisms through which TAMs induce EMT, including cytokines, chemokines and stromal cross-talking. Following this, the review explores TAM-induced EMT features in select cancer types with notable EMT characteristics, highlighting recent insights and the impact of TAMs on cancer progression. Finally, the review concludes with a discussion of potential therapeutic targets and strategies aimed at mitigating TAM infiltration and disrupting the EMT signaling network, thereby underscoring the potential of emerging treatments to combat TAM-mediated EMT in cancer. This comprehensive analysis reaffirms the necessity for continued exploration into TAMs’ regulatory roles within cancer biology to refine therapeutic approaches and improve patient outcomes.
Atlas of mildly and highly insoluble matrisome driving liver fibrosis
Authors: Zhang Wen , Zhang Ning , Wu Wenyue , Li Hong , You Hong , Chen Wei
Published: September 2024

The excessive deposition and cross-linking of core matrisome components typically result in abnormal remodeling of the extracellular matrix (ECM), leading to increased liver stiffness and worsening liver fibrosis. Exploring the biochemical properties of the ECM scaffold can deepen our understanding of the pathological mechanisms driving liver fibrosis and potentially facilitate the identification of therapeutic targets. While traditional sodium dodecyl sulfate (SDS)-based liver decellularization followed by proteomics can uncover the matrisome components within the ECM scaffold, it lacks the ability to reveal physicochemical characteristics like solubility. In our present study, using adult mouse liver as an example, we introduced a novel two-step workflow that combines our previously enhanced SDS (ESDS) decellularization with the conventional SDS method, enabling the identification of matrisome members with mild and/or high solubilities. Through this approach, we visualized the atlas of the mildly and highly insoluble matrisome contents in the adult mouse liver, as well as the regulatory network of highly insoluble matrisome that largely governs liver stiffness. Given the strong correlation between increased matrisome insolubility and heightened ECM stiffness, we believe that this methodology holds promise for future research focused on liver stiffness.
Metabolic and hormonal responses to acute high-load resistance exercise in normobaric hypoxia using a saturation clamp
Authors: Jiang Guole , Qin Shuang , Yan Bing , Girard Olivier
Published: September 2024

Introduction

We assessed metabolic and hormonal responses to high-load resistance exercise under varying normobaric hypoxia conditions with a saturation clamp.

Methods

Employing a counterbalanced, crossover test design, ten well-trained men participated in three exercise trials with normoxic or hypoxic gas mixtures to maintain arterial oxygen saturation at −90% and 80% [moderate (MH) and severe (SH) hypoxia, respectively]. The resistance exercise regimen comprised five sets of 10 repetitions of barbell back squats at 70% of one repetition maximum, with 1-min rest between sets. Metabolic and hormonal responses were measured before normoxia or hypoxia exposures (Pre 1), 15 min after the exposures (Pre 2), and at 0-, 15-, and 30-min post-exercises (T0, T15, and T30, respectively).

Results

Compared to Pre 2, blood lactate concentrations and growth hormone values were elevated at T0, T15, and T30 (p ≤ 0.001), while testosterone values increased at T0 in all conditions (p ≤ 0.009). Epinephrine values increased significantly from Pre 2 to T0 in SH only (p < 0.001). SH had significantly higher blood lactate concentrations (p = 0.023), growth hormone (p = 0.050), and epinephrine (p = 0.020) values at T30 compared to NM. Cortisol values were elevated above Pre 2 at T15 in MH and SH, while lower testosterone values were noted at T0 and T15 for SH compared to NM and MH (all p ≤ 0.05).

Discussion

Severe simulated hypoxia, achieved through a saturation clamp during barbell back squats, may enhance metabolic and hormonal responses, particularly 30 min post-session. Nevertheless, the acute effects of hypoxia exposure seem to be overridden by the impact of high-load resistance exercise.