bluuebunny/crossref_metadata_2025 huggingface dataset:
Engaging innate immunity for targeting the epidermal growth factor receptor: Therapeutic options leveraging innate immunity versus adaptive immunity versus inhibition of signaling
Authors: Hintzen Gabriele , Dulat Holger J. , Rajkovic Erich
Published: September 2022

The epidermal growth factor receptor (EGFR) is a key player in the normal tissue physiology and the pathology of cancer. Therapeutic approaches have now been developed to target oncogenic genetic aberrations of EGFR, found in a subset of tumors, and to take advantage of overexpression of EGFR in tumors. The development of small-molecule inhibitors and anti-EGFR antibodies targeting EGFR activation have resulted in effective but limited treatment options for patients with mutated or wild-type EGFR-expressing cancers, while therapeutic approaches that deploy effectors of the adaptive or innate immune system are still undergoing development. This review discusses EGFR-targeting therapies acting through distinct molecular mechanisms to destroy EGFR-expressing cancer cells. The focus is on the successes and limitations of therapies targeting the activation of EGFR versus those that exploit the cytotoxic T cells and innate immune cells to target EGFR-expressing cancer cells. Moreover, we discuss alternative approaches that may have the potential to overcome limitations of current therapies; in particular the innate cell engagers are discussed. Furthermore, this review highlights the potential to combine innate cell engagers with immunotherapies, to maximize their effectiveness, or with unspecific cell therapies, to convert them into tumor-specific agents.
PD-1/PD-L1 immune-checkpoint blockade induces immune effector cell modulation in metastatic non-small cell lung cancer patients: A single-cell flow cytometry approach
Authors: Fameli Antonella , Nardone Valerio , Shekarkar Azgomi Mojtaba , Bianco Giovanna , Gandolfo Claudia , Oliva Bianca Maria , Monoriti Marika , Saladino Rita Emilena , Falzea Antonella , Romeo Caterina , Calandruccio Natale Daniele , Azzarello Domenico , Giannicola Rocco , Pirtoli Luigi , Giordano Antonio , Tassone Pierfrancesco , Tagliaferri Pierosandro , Cusi Maria Grazia , Mutti Luciano , Botta Cirino , Correale Pierpaolo
Published: September 2022

Peripheral immune-checkpoint blockade with mAbs to programmed cell death receptor-1 (PD-1) (either nivolumab or pembrolizumab) or PD-Ligand-1 (PD-L1) (atezolizumab, durvalumab, or avelumab) alone or in combination with doublet chemotherapy represents an expanding treatment strategy for metastatic non-small cell lung cancer (mNSCLC) patients. This strategy lays on the capability of these mAbs to rescue tumor-specific cytotoxic T lymphocytes (CTLs) inactivated throughout PD-1 binding to PD-L1/2 in the tumor sites. This inhibitory interactive pathway is a physiological mechanism of prevention against dangerous overreactions and autoimmunity in case of prolonged and/or repeated CTL response to the same antigen peptides. Therefore, we have carried out a retrospective bioinformatics analysis by single-cell flow cytometry to evaluate if PD-1/PD-L1-blocking mAbs modulate the expression of specific peripheral immune cell subsets, potentially correlated with autoimmunity triggering in 28 mNSCLC patients. We recorded a treatment-related decline in CD4+ T-cell and B-cell subsets and in the neutrophil-to-lymphocyte ratio coupled with an increase in natural killer T (NKT), CD8+PD1+ T cells, and eosinophils. Treatment-related increase in autoantibodies [mainly antinuclear antibodies (ANAs) and extractable nuclear antigen (ENA) antibodies] as well as the frequency of immune-related adverse events were associated with the deregulation of specific immune subpopulations (e.g., NKT cells). Correlative biological/clinical studies with deep immune monitoring are badly needed for a better characterization of the effects produced by PD-1/PD-L1 immune-checkpoint blockade.
A new core–shell-type nanoparticle loaded with paclitaxel/norcantharidin and modified with APRPG enhances anti-tumor effects in hepatocellular carcinoma
Authors: Xie Ming-Hua , Fu Zai-Lin , Hua Ai-Lian , Zhou Ji-Fang , Chen Qian , Li Jian-Bo , Yao Shen , Cai Xin-Jun , Ge Min , Zhou Li , Wu Jia
Published: September 2022

Nanoparticle delivery systems have been shown to improve the therapeutic efficacy of anti-cancer drugs, including a variety of drugs for the treatment of hepatocellular carcinoma (HCC). However, the current systems show some limitations, and the delivery of more effective nanoparticle systems for anti-HCC drugs with better targeting ability are needed. Here, we created paclitaxel (PTX)/norcantharidin (NCTD)-loaded core–shell lipid nanoparticles modified with a tumor neovasculature-targeted peptide (Ala-Pro-Arg-Pro-Gly, APRPG) and investigated their anti-tumor effects in HCC. Core–shell-type lipid nanoparticles (PTX/NCTD-APRPG-NPs) were established by combining poly(lactic-co-glycolic acid) (PLGA)-wrapped PTX with phospholipid-wrapped NCTD, followed by modification with APRPG. For comparison, PTX-loaded PLGA nanoparticles (PTX-NPs) and PTX/NCTD-loaded core–shell-type nanoparticles without APRPG (PTX/NCTD-NPs) were prepared. The in vitro and in vivo anti-tumor effects were examined in HepG2 cells and tumor-bearing mice, respectively. Morphological and release characterization showed that PTX/NCTD-APRPG-NPs were prepared successfully and achieved up to 90% release of PTX in a sustained manner. Compared with PTX/NCTD-NPs, PTX/NCTD-APRPG-NPs significantly enhanced the uptake of PTX. Notably, the inhibition of proliferation and migration of hepatoma cells was significantly higher in the PTX/NCTD-APRPG-NP group than those in the PTX-NP and PTX/NCTD-NP groups, which reflected significantly greater anti-tumor properties as well. Furthermore, key molecules in cell proliferation and apoptosis signaling pathways were altered most in the PTX/NCTD-APRPG-NP group, compared with the PTX-NP and PTX/NCTD-NP groups. Collectively, PTX/NCTD-loaded core–shell lipid nanoparticles modified with APRPG enhance the effectiveness of anti-HCC drugs and may be an effective system for the delivery of anti-HCC drugs.
Icariin attenuates the tumor growth by targeting miR-1-3p/TNKS2/Wnt/β-catenin signaling axis in ovarian cancer
Authors: Fu Yanjin , Liu Haiquan , Long Mengsha , Song Linliang , Meng Zuyu , Lin Shaozi , Zhang Yiyao , Qin JiaJia
Published: September 2022

Purpose

Despite various therapy advances, ovarian cancer remains an incurable disease for which survival rates have only modestly improved. Natural products are important sources of anti-cancer lead compounds. Icariin exhibited broad anti-cancer efficacy. However, the mechanism of icariin against ovarian cancer is poorly elucidated.

Methods

Cell viability was detected to evaluate the effect of icariin on SKOV-3 cells. The cell cycle and apoptosis were analyzed. The transcript of SKOV-3 cells was profiled by RNA-seq. GSEA and DEGs analyses were performed to interpret gene expression data. Western blot and TOP/FOP flash assay were applied to detect Wnt/β-catenin signaling. MiRDB database and dual-luciferase reporter assay was applied to study the regulation of miR-1-3p on TNKS2. Anti-tumor efficacy of icariin was evaluated by xenograft mouse model. Immunohistochemistry was performed with antibodies against Ki67.

Results

Icariin significantly suppressed the proliferation of SKOV-3 cells. Furthermore, icariin stalled cell cycle and induced apoptosis by blocking TNKS2/Wnt/β-catenin pathway through upregulating the level of miR-1-3p. Finally, icariin dramatically suppressed tumor growth in vivo.

Conclusions

In this study, we demonstrated for the first time that icariin significantly attenuated the growth of ovarian tumor in xenograft mouse model. Furthermore, we systematically revealed that icariin attenuates the tumor progression by suppressing TNKS2/Wnt/β-catenin signaling via upregulating the level of miR-1-3p in ovarian cancer with transcriptome analysis.
Conversion therapy from unresectable stage IIIC non-small-cell lung cancer to radical surgery via anti-PD-1 immunotherapy combined with chemotherapy and anti-angiogenesis: A case report and literature review
Authors: Jia Guohua , Zhou Shuimei , Xu Tangpeng , Huang Yabing , Li Xiangpan
Published: September 2022

The prognosis of patients with stage IIIC non-small-cell lung cancer (NSCLC) is poor due to the loss of surgical treatment opportunities. Improving the prognosis of these patients with IIIC NSCLC urgently needs to be addressed. Here, we report a stage IIIC (T4N3M0 IIIC (AJCC 8th)) NSCLC patient treated with 2 cycles of anti-PD-1 immunotherapy combined with chemotherapy and anti-angiogenesis therapy; after two cycles of treatment, the patient achieved a partial response and obtained the opportunity for surgical treatment. After the operation, the patient achieved a pathological complete response and successfully transformed from unresectable stage IIIC lung cancer to radical surgery (ypT0N0M0). Our study is expected to provide new ideas for treating patients with unresectable stage IIIC NSCLC in the future.
Platelet detection as a new liquid biopsy tool for human cancers
Authors: Chen Maoshan , Hou Lijia , Hu Lanyue , Tan Chengning , Wang Xiaojie , Bao Peipei , Ran Qian , Chen Li , Li Zhongjun
Published: September 2022

Cancer is still a leading cause of death worldwide and liquid biopsy is a powerful tool that can be applied to different stages of cancer screening and treatment. However, as the second most abundant cell type in the bloodstream, platelets are isolated through well-established and fast methods in clinic but their value as a BioSource of cancer biomarkers is relatively recent. Many studies demonstrated the bidirectional interaction between cancer cells and platelets. Platelets transfer various proteins (e.g., growth factors, cytokine, chemokines) and RNAs (e.g., mRNA, lncRNA, miRNA, circRNA) into the tumor cells and microenvironment, leading the stimulation of tumor growth and metastasis. In turn, the platelet clinical characteristics (e.g., count and volume) and contents (e.g., RNA and protein) are altered by the interactions with cancer cells and this enables the early cancer detection using these features of platelets. In addition, platelet-derived microparticles also demonstrate the prediction power of being cancer biomarkers. In this review, we focus on the clinical applications of platelet detection using the platelet count, mean platelet volume, platelet RNA and protein profiles for human cancers and discuss the gap in bringing these implementations into the clinic.
The FLOTAC basic technique as a new extraction method for root-knot nematodes (Meloidogyne spp.) from soil and roots
Authors: Troccoli Alberto , d’Errico Giada , D’Addabbo Trifone , Sasanelli Nicola , Bosco Antonio , Maurelli Maria P. , Rinaldi Laura , Cringoli Giuseppe
Published: September 2022

FLOTAC Techniques have been widely acknowledged as an effective method for the extraction of human and animal parasites. The present study is the first application of FLOTAC basic technique (FBT) for the extraction of phytoparasitic nematodes from soil and infested plant roots. Eggs and second stage juveniles (J2) of the root-knot nematode Meloidogyne incognita were extracted from infested soil and tomato roots either by FBT and conventional nematode extraction methods, such as centrifugal flotation and root maceration techniques, respectively. The number of M. incognita J2 and eggs extracted from soil by FBT was always significantly higher compared to the extraction with the centrifugal flotation method, averaging 277 vs 35 eggs and J2 mL-1 soil. Conversely, no significant differences were observed between FBT and the root maceration technique in the extraction of eggs and J2 from tomato roots. Results demonstrated that FBT can be highly effective also for the extraction of phytoparasitic nematodes. Due to its accuracy and sensitivity, FBT seems particularly suitable for nematode surveys in wide geographical areas, where an accurate and rapid detection of present phytoparasitic nematofauna is required.
Prevalence and correlates of severe under-5 child anthropometric failure measured by the composite index of severe anthropometric failure in Bangladesh
Authors: Chowdhury Mohammad Rocky Khan , Khan Hafiz T. A. , Rashid Mamunur , Mondal Md. Nazrul Islam , Bornee Farzana Akhter , Billah Baki
Published: September 2022

Background

Although Bangladesh has made noticeable progress in reducing the prevalence of stunting, wasting, and being underweight among under-5 children, it has not been very successful in reducing overall severe anthropometric failure (SAF) among them. Therefore, the study aims to identify the prevalence and risk factors of SAF measured by the Composite Index of Severe Anthropometric Failure (CISAF) among under-5 children in Bangladesh.

Methods

Data was drawn from a cross-sectional Bangladesh Demographic Health Survey (BDHS) conducted in 2017–2018. A bivariate analysis (Chi-square test) and logistic regression analysis were used to estimate the unadjusted, and age and sex-adjusted prevalence of SAF. Odds ratio (OR) and confidence interval (CI) were assessed using logistic regression analysis to identify the various risk factor of SAF.

Results

The overall adjusted prevalence of under-5 child SAF was 11.3% (95% CI: 10.6–12.0) and it was highly prevalent among children of uneducated mothers (adjusted, 22%, 95% CI: 17.3–26.8). The key factors associated with SAF were children in the age group 24–35 months (OR: 2.43, 95% CI: 1.83–3.23), children born with low birth weight (OR: 3.14, 95% CI: 2.24–4.97), children of underweight mothers (OR: 1.82, 95% CI: 1.44–2.29), children of parents with no formal education (OR: 2.28, 95% CI: 1.56–3.31) and children from lower socio-economic status (OR: 2.25, 95% CI: 1.55–3.26).

Conclusion

Prioritizing and ensuring context-specific interventions addressing individual, community, public policy, and environment level risk factors from policy level to implementation to reduce structural and intermediary determinants of under-5 SAF.
Molecular characterization of PI*Shangzhou, a SERPINA1 allele from continental China encoding a defective alpha-1-antitrypsin
Authors: Hernández-Pérez José M. , González Carracedo Mario A. , García Angelines Concepción , Pérez José A. Pérez
Published: September 2022

Alpha-1-antitrypsin deficiency (AATD) is a heritable condition that predisposes to respiratory and hepatic complications. Screenings in East Asia human populations for the AATD alleles most commonly found among Caucasians have yielded poor outcomes. Serum alpha-1-antitrypsin (AAT) levels, AAT phenotypes, and sequences of SERPINA1 gene were examined in a Chinese child with a moderate deficit of serum AAT, who had suffered several episodes of liver disease, as well as in his first-order relatives. Results allowed the identification of PI*Shangzhou, a novel SERPINA1 defective allele, which has been characterized by a L276R substitution, found in a SERPINA1-M3 genetic background. Moreover, potential effects of PI*Shangzhou mutation over the AAT structure were studied by 3D homology modeling. The presence of an arginine residue at position 276 could destabilize the tertiary structure of AAT, since it occurs at a highly conserved hydrophobic cavity in the protein surface, and very close to two positively-charged lysine residues. Attending to the frequency of R276 variant reported in databases for individuals of East Asian ancestry, the PI*Shangzhou allele may explain the global prevalence of the PiS phenotype observed in China.
Delays in diagnosis and treatment initiation for congenital cytomegalovirus infection - Why we need universal screening
Authors: Alifieraki Styliani , Payne Helen , Hathaway Chantal , Tan Rachel Wei Ying , Lyall Hermione
Published: September 2022

Introduction

Congenital cytomegalovirus (cCMV) is the leading cause of neurodevelopmental and hearing impairment from in-utero infection. Late diagnosis results in limited treatment options and may compromise long-term outcome.

Methods

A retrospective audit of infants with cCMV referred to a Tertiary Pediatric Infectious Diseases center from 2012–2021. Data collected included timing of diagnostics, treatment initiation and reasons for delays.

Results

90 infants with confirmed cCMV were included, 46/90 (51%) were symptomatic at birth. Most common reasons for diagnostics in asymptomatic infants were failed newborn hearing screening (17/44, 39%) and antenatal risk-factors (14/44, 32%). Median age at cCMV diagnosis was 3 (range 0–68) and 7 (0–515) days, with median referral age 10 (1–120) and 22 (2–760) days for symptomatic and asymptomatic infants respectively. There was a significant risk of delay in diagnosis (>21 days) for asymptomatic infants [RR 2.93 (1.15–7.45); p = 0.02]. Of asymptomatic infants who received treatment, 13/24 (54%) commenced it within 28 days of life, a significant delay in treatment compared to 30/36 (83%) symptomatic infants [RR 2.75 (1.18–6.43); p = 0.02]. The commonest reason for delayed treatment initiation was delayed first diagnostic test for both symptomatic 4/6 (67%) and asymptomatic infants 9/11 (82%).

Conclusions

Delays in diagnosis and treatment for cCMV are unacceptably frequent and significantly higher in asymptomatic infants. Our study highlights the need for increased awareness among healthcare professionals, reconsideration of age-targets for Newborn Hearing Screening, and research that addresses the barriers to implementation of universal screening, which would ultimately facilitate prompt diagnosis and management of all infants with cCMV.
Sea cucumber-derived compounds for treatment of dyslipidemia: A review
Authors: Lin Ping , Shen Nuo , Yin Fan , Guo Shou-Dong
Published: September 2022

Dyslipidemias are disorders of plasma levels of lipids, such as elevated levels of total cholesterol and triglyceride, that are associated with various human diseases including cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Statins are the first-line drugs for treatment of dyslipidemia. However, a substantial proportion of patients cannot reach the recommended LDL-c level even with the highest tolerated doses of statins, and there is no available drug specifically for NAFLD therapy. Sea cucumbers are one of the widely distributed invertebrates, and are an important resource of food and medicine. Sea cucumbers have many valuable nutrients including saponins, fatty acids, phospholipids, cerebrosides, sulfated polysaccharides, as well as proteins and peptides. In recent years, these natural products derived from sea cucumbers have attracted attentions for treatment of CVD and NAFLD because of their lipid-lowering effect and low toxicity. However, the hypolipidemic mechanisms of action and the structure-activity relationship of these bioactive components have not been well-documented in literature. This review article summarizes the signaling pathways and the potential structure-activity relationship of sea cucumber-derived bioactive compounds including saponins, lipids, carbohydrates as well as peptides and proteins. This article will provide information useful for the development of sea cucumber-derived lipid-lowering compounds as well as for investigation of hypolipidemic compounds that are derived from other natural resources.
Comprehensive comparison on the anti-inflammation and GC-MS-based metabolomics discrimination between Bupleuri chinense DC. and B. scorzonerifolium Willd
Authors: Zhao Mingming , Xiao Linxuan , Linghu Ke-Gang , Zhao Guanding , Chen Qiling , Shen Liyu , Dar Parsa , Chen Meiwan , Hu Yuan , Zhang Jinming , Yu Hua
Published: September 2022

Bupleuri Radix (BR) is a traditional Chinese medicine and widely used for cold and fever, influenza, inflammation, hepatitis and menstrual diseases. Two authentic medicinal plants of Bupleuri chinense DC. (Beichaihu, BCH) and B. scorzonerifolium Willd. (Nanchiahu, NCH) are recommended by the current Chinese Pharmacopoeia for BR. In the present study, the comparative investigations on the anti-inflammatory effects and gas chromatography-mass spectrometry (GC-MS)-based metabolomics for the species discrimination of BCH and NCH were conducted and reported. The in vitro evaluations indicated that the supercritical fluid extracts (SFEs) (IC50 of 6.39 ± 0.52 and 1.32 ± 0.05 mg (herb)/mL for BCH and NCH) were determined to be more potent than those of the hydro-distillation extracts (HDEs) (IC50 of 203.90 ± 8.08 and 32.32 ± 2.27 mg (herb)/mL for BCH and NCH) against LPS-induced inflammation in RAW264.7 macrophages. The higher anti-inflammatory effects of NCH were associated to its different chemical compositions to the BCH as characterized by the GC-MS analysis. Furthermore, based on the metabolomics and deep chemometric approaches, a minimum combination containing 15 chemical markers was optimized from the identified components and successfully applied for the species discrimination of BCH and NCH. This study not only helps to comparative understand BCH and NCH both in phytochemistry and pharmacology, but also provides the potential chemical markers for improvement of methods for the quality control of BCH and NCH.
Peripheral and intestinal mucosal-associated invariant T cells in premature infants with necrotizing enterocolitis
Authors: Tian Jiayi , Yan Chaoying , Jiang Yanfang , Zhou Haohan , Li Liyuan , Shen Jingjing , Wang Jian , Sun Hongyu , Yang Guang , Sun Wei
Published: September 2022

Background: Necrotizing enterocolitis (NEC) is a potentially fatal inflammatory gastrointestinal disease in preterm infants with unknown pathogenesis. Mucosal-associated invariant T (MAIT) cells primarily accumulate at sites where exposure to microbes is ubiquitous and regulate immunological responses. As the implications of these cells in NEC development in premature infants remain unknown, we investigated the role and characteristics of MAIT cells in NEC pathogenesis.

Methods: The percentage of different MAIT cell subsets in peripheral blood samples of 30 preterm infants with NEC and 22 control subjects was estimated using flow cytometry. The frequency of MAIT cells in the intestinal tissues of five NEC patients and five control subjects was also examined. The level of serum cytokines was estimated using cytometric bead array. Potential associations between the different measurements were analyzed using the Spearman’s correlation test.

Results: Compared with controls, the NEC patients were found to have significantly reduced percentages of circulating CD161+ CD3+ CD8αα+ T cells and CD161+ CD3+ TCRγδ-TCRVa7.2+ MAIT cells. In the intestinal tissues, the percentage of MAIT cells was significantly higher in samples from the NEC patients than the controls. Furthermore, the percentage of circulating MAIT cells in the peripheral blood samples was inversely correlated with that in the intestinal tissues of the NEC patients. The percentage of CD8αα+ MAIT cells was found to be significantly reduced in both peripheral blood and intestinal tissues of NEC patients. Following treatment, the frequency of circulating MAIT cells significantly increased in NEC patients and reached a level similar to that in the control subjects. However, there was no difference in the percentage of circulating CD8αα+ MAIT cells before and after treatment in the NEC patients.

Conclusion: Our results suggested that during the development of NEC MAIT cells accumulate in the inflammatory intestinal tissues, while the percentage of CD8aa+ MAIT cells is significantly decreased, which may lead to the dysfunction of MAIT cells in gut immunity.
Nucleophosmin 1 is a prognostic marker of gastrointestinal cancer and is associated with m6A and cuproptosis
Authors: Liu Xu-Sheng , Liu Chao , Zeng Jing , Zeng Dao-Bing , Chen Yi-Jia , Tan Fan , Gao Yan , Liu Xiao-Yu , Zhang Yu , Zhang Yao-Hua , Pei Zhi-Jun
Published: September 2022

Background: NPM1 is highly expressed in a variety of solid tumors and promotes tumor development. However, there are few comprehensive studies on NPM1 analysis in gastrointestinal cancer.

Methods: We used bioinformatics tools to study the expression difference of NPM1 between gastrointestinal cancer and control group, and analyzed the relationship between its expression level and the diagnosis, prognosis, functional signaling pathway, immune infiltration, m6A and cuproptosis related genes of gastrointestinal cancer. At the same time, the expression difference of NPM1 between esophageal carcinoma (ESCA) samples and control samples was verified by in vitro experiments.

Results: NPM1 was overexpressed in gastrointestinal cancer. In vitro experiments confirmed that the expression of NPM1 in ESCA samples was higher than that in normal samples. The expression of NPM1 has high accuracy in predicting the outcome of gastrointestinal cancer. The expression of NPM1 is closely related to the prognosis of multiple gastrointestinal cancers. Go and KEGG enrichment analysis showed that NPM1 co-expressed genes involved in a variety of biological functions. NPM1 expression is potentially associated with a variety of immune cell infiltration, m6A and cuproptosis related genes in gastrointestinal cancers.

Conclusion: NPM1 can be used as a diagnostic and prognostic marker of gastrointestinal cancer, which is related to the immune cell infiltration and the regulation of m6A and cuproptosis.
The effect of SSRIs on Semen quality: A systematic review and meta-analysis
Authors: Xu Jiarong , He Kancheng , Zhou Yihong , Zhao Liangyu , Lin Yuteng , Huang Zihao , Xie Nengqing , Yue Jihui , Tang Yuxin
Published: September 2022

Selective serotonin reuptake inhibitors (SSRIs) are widely used for a variety of diseases, and their impact on semen quality is unclear. We performed a systematic search in PubMed and Embase, and after a strict screening, we included 4 studies with a total of 222 male participants. In result, SSRIs reduced normal sperm morphology (95% CI [−16.29, −3.77], p = 0.002), sperm concentration (95%CI [−43.88, −4.18], p = 0.02), sperm motility (95%CI [−23.46, −0.47], p = 0.04) and sperm DNA fragmentation index (DFI) (95% CI [6.66,21.93], p = 0.0002), without a statistically significant effect on semen volume (95%CI [−0.75,0.65], p = 0.89). Moreover, the impact on both sperm morphology and sperm concentration were observed within the 3-month period of SSRIs use. In general, our meta-analysis showed that SSRIs have a negative effect on semen quality. More larger, randomized, well-controlled clinical studies should be conducted to support our conclusion.
Initial sirolimus dosage recommendations for pediatric patients with PIK3CD mutation-related immunodeficiency disease
Authors: Chen Xiao , Wang Jinglin , Lan Jianger , Ge Xilin , Xu Hong , Zhang Yu , Li Zhiping
Published: September 2022

Sirolimus is used to treat pediatric patients with PIK3CD mutation-related immunodeficiency disease. However, the initial dosages of sirolimus remain undecided. The present study aims to explore initial dosages in pediatric patients with PIK3CD mutation-related immunodeficiency disease. Pediatric patients with this disease were analyzed using the population pharmacokinetic (PPK) model and the Monte Carlo simulation. Body weight and concomitant use of posaconazole were included in the final PPK model, where, under the same weight, clearances of sirolimus were 1 : 0.238 between children without and children with posaconazole. Without posaconazole, the initial dosages of sirolimus were 0.07, 0.06, 0.05, and 0.04 mg/kg/day for body weights of 10–14, 14–25, 25–50, and 50–60 kg, respectively. With posaconazole, the initial dosages of sirolimus were 0.02 mg/kg/day for body weights of 10–60 kg. This is the first attempt to build a sirolimus PPK model for recommending initial dosages in children with PIK3CD mutation-related immunodeficiency disease, thereby providing a reference for individualized clinical drug administration.
Control of aging by the renin–angiotensin system: a review of C. elegans, Drosophila, and mammals
Authors: Egan Brian M. , Scharf Andrea , Pohl Franziska , Kornfeld Kerry
Published: September 2022

The free-living, non-parasitic nematode Caenorhabditis elegans is a premier model organism for the study of aging and longevity due to its short lifespan, powerful genetic tools, and conservation of fundamental mechanisms with mammals. Approximately 70 percent of human genes have homologs in C. elegans, including many that encode proteins in pathways that influence aging. Numerous genetic pathways have been identified in C. elegans that affect lifespan, including the dietary restriction pathway, the insulin/insulin-like growth factor (IGF) signaling pathway, and the disruption of components of the mitochondrial electron transport chain. C. elegans is also a powerful system for performing drug screens, and many lifespan-extending compounds have been reported; notably, several FDA-approved medications extend the lifespan in C. elegans, raising the possibility that they can also extend the lifespan in humans. The renin–angiotensin system (RAS) in mammals is an endocrine system that regulates blood pressure and a paracrine system that acts in a wide range of tissues to control physiological processes; it is a popular target for drugs that reduce blood pressure, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). Emerging evidence indicates that this system influences aging. In C. elegans, decreasing the activity of the ACE homolog acn-1 or treatment with the ACE-inhibitor Captopril significantly extends the lifespan. In Drosophila, treatment with ACE inhibitors extends the lifespan. In rodents, manipulating the RAS with genetic or pharmacological interventions can extend the lifespan. In humans, polymorphisms in the ACE gene are associated with extreme longevity. These results suggest the RAS plays a conserved role in controlling longevity. Here, we review studies of the RAS and aging, emphasizing the potential of C. elegans as a model for understanding the mechanism of lifespan control.
Bibliometric and visual analysis of nephrotoxicity research worldwide
Authors: He Tianmu , Ao Jingwen , Duan Cancan , Yan Rong , Li Xiaomei , Liu Liu , Zhang Jianyong , Li Xiaofei
Published: September 2022

Background: Nephrotoxicity of drugs contributes to acute kidney injury with high mortality and morbidity, which crucially limits the application and development of drugs. Although many publications on nephrotoxicity have been conducted globally, there needs to be a scientometric study to systematically analyze the intellectual landscape and frontiers research trends in the future.

Methods: Publications on nephrotoxicity from 2011 to 2021 were collected to perform bibliometric visualization using VOSviewer, CiteSpace, and Scimago Graphica software based on the Web of Science Core Collection.

Results: A total of 9,342 documents were analyzed, which were primarily published in the United States (1,861), China (1,724), and Egypt (701). For institutions, King Saud University (166) had the most publications; Food and Chemical Toxicology, PLOS One, and Antimicrobial Agents and Chemotherapy were productive journals, primarily concentrating on the mechanisms of nephrotoxicity and renoprotective in cisplatin and antibiotics, especially in oxidative stress. Burst detection suggested that cisplatin, piperacillin-tazobactam, vancomycin-induced nephrotoxicity, antioxidants, and new biomaterials are frontiers of research.

Conclusion: This study first provides an updated perspective on nephrotoxicity and renoprotective strategies and mechanisms. This perspective may benefit researchers in choosing suitable journals and collaborators and assisting them in the deep understanding of the nephrotoxicity and renoprotective hotspots and frontiers.
The current status of old traditional medicine introduced from Persia to China
Authors: Shi Jinmin , Yang Yifan , Zhou Xinxin , Zhao Lijun , Li Xiaohua , Yusuf Abdullah , Hosseini Mohaddeseh S. M. Z. , Sefidkon Fatemeh , Hu Xuebo
Published: September 2022

Traditional Chinese medicine (TCM) includes over ten thousand herbal medicines, some of which were introduced from outside countries and territories. The Silk Road enabled the exchange of merchandise such as teas, silks, carpets, and medicines between the East and West of the Eurasia continent. During this time, the ‘Compendium of Materia Medica’ (CMM) was composed by a traditional medicine practitioner, Shizhen Li (1,518–1,593) of the Ming Dynasty. This epoch-making masterpiece collected knowledge of traditional medical materials and treatments in China from the 16th century and before in utmost detail, including the origin where a material was obtained. Of 1892 medical materials from the CMM, 46 came from Persia (now Iran). In this study, the basic information of these 46 materials, including the time of introduction, the medicinal value in TCM theory, together with the current status of these medicines in China and Iran, are summarized. It is found that 20 herbs and four stones out of the 46 materials are registered as medicinal materials in the latest China Pharmacopoeia. Now most of these herbs and stones are distributed in China or replacements are available but saffron, ferula, myrrh, and olibanum are still highly dependent on imports. This study may contribute to the further development, exchange, and internationalization of traditional medicine of various backgrounds in the world, given the barriers of transportation and language are largely eased in nowadays.
Effects of postoperative adjuvant steroid therapy on the outcomes of biliary atresia: A systematic review and updated meta-analysis
Authors: Yang Chang-zhen , Zhou Yan , Ke Meng , Gao Ru-yue , Ye Shi-ru , Diao Mei , Li Long
Published: September 2022

Background: Postoperative adjuvant steroid therapy is regarded as the conventional treatment for patients with biliary atresia (BA) who have undergone Kasai portoenterostomy (KP). However, whether the steroid therapy can improve BA outcomes is controversial. This meta-analysis aimed to evaluate the effects of adjuvant steroid therapy on the surgical prognosis of BA.

Methods: We searched related studies published in PubMed, Embase, Web of Science, Cochrane, and the Chinese National Knowledge Infrastructure database up to May 2022. Data on the effect of steroid use on the clinical prognosis of the patients, including the jaundice clearance rate (JCR), native liver survival rate (NLSR) at 6, 12, and 24 months after KP, and the incidence of cholangitis, were extracted. Subgroup analyses based on age at KP, administration method, initial dosage, and steroid type were conducted. Statistical analysis was conducted using Stata/SE 12.0.

Results: Eleven articles (a total of 1,032 patients) were included in the present meta-analysis. The results demonstrated that postoperative adjuvant steroid therapy improved JCR at the 6/12/24-month follow-up (RR: 1.35, 95% CI: 1.18–1.55, p < 0.001; RR:1.49, 95% CI, 1.12–1.99, p = 0.006; RR: 1.41, 95% CI: 1.14–1.75, p = 0.002) and improved NLSR at the 24-month follow-up (RR: 1.31, 95% CI: 1.03–1.68, p = 0.028). However, steroids could not significantly improve NLSR at the 6/12-month follow-up (RR: 1.06; 95% CI: 0.98–1.15; p = 0.17; RR: 1.22; 95% CI: 0.97–1.54; p = 0.095), and might not decrease the incidence of postoperative cholangitis (RR: 0.78, 95% CI: 0.60–1.01, p = 0.058). Furthermore, subgroup analyses confirmed that three variables (age at KP, administration method, and initial dosage) could affect the efficacy of steroids in BA patients.

Conclusion: Postoperative adjuvant steroid therapy can significantly improve bile flow. The superiority of steroid therapy was more remarkable in patients aged ≤70 days at KP than in those aged >70 days. Additionally, intravenous followed by oral steroid administration method and medium initial dosage seemed to have the more reliable efficiency on bile flow. And patients treated by steroid had better long-term (24-month) native liver survival, but there is no significant effect on short-term native liver survival and postoperative cholangitis. Further studies are warranted.
A graphene-based THz metasurface sensor with air-spaced structure
Authors: Hu Hui , Qi Bin , Zhao Yufan , Zhang Xiaoju , Wang Yue , Huang Xinning
Published: September 2022

Owing to the unique electromagnetic response ability, electromagnetic metasurface have potential applications in medical, imaging, sensing, and other fields. In this paper, a graphene-based THz metasurface sensor with an air spacer layer is designed by combining the advantages of the air spacer structure and the dynamic tunability of graphene materials. The proposed metasurface sensor consists of six layers, which are silicon dioxide (SiO2) substrate, metal reflector, air layer, graphene metasurface etched with microstructure, ion-gel layer and silicon dioxide dielectric layer from bottom to top. A comprehensive study of the absorption properties and sensing performance are carried out which is simulated and analyzed with the help of CST Microwave Studio software. The calculation results show that the two obvious resonance absorption peaks located at 0.95 THz and 1.53 THz with absorption of 94.9% and 79%, respectively, and there is a good linear relationship between the absorption peak and dielectric parameters of analyte. The frequency shift sensitivity of the two resonance peaks M1 and M2 can reach 450 GHz/RIU and 717 GHz/RIU, respectively. By changing the thickness of the air layer, when the two resonance peaks M1 and M2 reach the maximum absorption at h2=140 μm and h2=280 μm, respectively, the frequency shift sensitivity is still as high as close to 450 GHz/RIU. The influence of structure parameters and incident angle on the absorption spectrum shows that the proposed structure has good stability and reliability. The proposed graphene-based absorption sensor has good biocompatibility, broadening the application range of terahertz functional devices.
Review of the development of the hydrogen maser technique and a brief introduction to its space applications
Authors: Dai Jiayu , Liu Tiexin , Cai Yong , Chen Zhichun , Li Qi
Published: September 2022

Since 1960, when the first hydrogen frequency standard, the microwave amplification by stimulated emission of radiation (maser), was developed in the laboratory of Norman Ramsey at Harvard University, the performance of its frequency stability and technique development have been closely related to scientific research. A variety of H-maser designs have been developed for the demands of space science applications, including the deep space network (DSN) and the gravity probe (GP) experiment. H-maser is one of three well-developed microwave atomic frequency standards and is widely used worldwide in both ground and on-board-based settings. Along with upgrades to the frequency stability performance of the H-maser, improved knowledge of the world has also been reported.
Increased seizure sensitivity in pregnant mice with genetic knockdown of acid sensing ion channel 2a is associated with impaired hippocampal inflammatory response
Authors: Jones-Muhammad Maria , Shao Qingmei , Warrington Junie P.
Published: September 2022

Acid sensing ion channels (ASICs) are mechano- and chemo-receptor channels that are activated by drops in extracellular pH as occurs after neurotransmission. In our previous study, we demonstrated that mice subjected to reduced utero-placental perfusion pressure during pregnancy, to mimic the pregnancy complication of preeclampsia, have reduced hippocampal expression of ASIC2a protein. We also showed that pregnant mice with heterozygous expression of ASIC2a (+/-) had increased sensitivity and severity to pentylenetetrazol-induced seizures; however, the mechanisms by which this occurs remain unclear. The purpose of this study was to investigate key molecular targets involving neurotransmission and inflammation that are differentially changed following seizure exposure in pregnant ASIC2a +/- mice. On gestational day 18.5, ASIC2a wild-type (+/+, n = 7) and +/- (n = 14) mice were injected with 40 mg/kg pentylenetetrazol and monitored for 30 min. Western blot and ELISA analysis revealed no difference in hippocampal synaptosome glutamate-related proteins but an increase in GABA concentration in pregnant +/- mice. Using ELISA and multiplex assays, we found a significant decrease in serum TNFα, and a decreased concentration of pro-inflammatory cytokines and chemokines in hippocampal cytosolic fraction. Significant reductions in IL-1β, IL-3, IL-12 (p70), eotaxin, interferon gamma, and macrophage inflammatory protein (MIP-1β), in the hippocampal cytosolic fractions of +/- mice were observed compared to +/+ mice. Additionally, there was no difference in hippocampal microglia density or activation in pregnant ASIC2a+/+ vs. +/- mice. These results support the hypothesis that pregnant mice with reduced ASIC2a may not be able to mount an inflammatory response following acute seizure exposure.
Human lymph node degeneration in the thoracic region: A morphometric and immunohistochemical analysis using surgically obtained specimens
Authors: Jin Zhe-Wu , Aoki Masaya , Ueda Kazuhiro , Kamimura Go , Takeda-Harada Aya , Murakami Gen , Sato Masami
Published: September 2022

Lymph node degeneration was examined in 539 mediastinal and intrapulmonary nodes removed from 78 patients, aged 49–82 years, without cancer metastasis. Medullary sinus hyalinization observed in 36.2% of the hilar and 38.5% of the interlobar nodes. Early and smaller lesions were eosinophilic and factor VIII-positive, whereas advanced and large lesions contained a bulky mass of collagenous fiber bundles with few slender cells positive for smooth muscle actin (SMA) and factor VIII, as well as anthracotic macrophages. Subcapsular sinus hyalinization, observed in 4.3% of hilar nodes, was detected as a thick fibrous layer (over 0.2 mm) between the surface cortex and the thickened capsule. The fibrous layer contained SMA-positive slender cells, whereas the thickened capsule contained fibers positive for elastin and factor VIII. These hyalinization lesions occupied 3.6% and 0.8% of the sectional areas of hilar and lower paratracheal nodes, respectively. Areas of early and small cortical degeneration, surrounded by fibers positive for SMA and vimentin, did not contain lymphocytes and macrophages, but contained abundant small stromal cells. Silver staining suggested that advanced cortical degeneration was composed of collagen fibrils other than type I. Fatty tissues, seen in 47.8% of hilar nodes, often extended into and replaced medullary sinus tissue. Island-like remnants of medullary sinuses in areas of fatty degeneration contained various stromal cells positive for SMA, elastin, factor VIII and/or CD34. These degenerative morphologies, however, did not correlate with either age or smoking index. The present cortical degeneration usually seemed to follow hyalinization, but both were likely to occur independently.
Mitochondrial fatty acid β-oxidation is important for normal osteoclast formation in growing female mice
Authors: Kushwaha Priyanka , Alekos Nathalie S. , Kim Soohyun P. , Li Zhu , Wolfgang Michael J. , Riddle Ryan C.
Published: September 2022

Skeletal remodeling is an energy demanding process that is linked to nutrient availability and the levels of metabolic hormones. While recent studies have examined the metabolic requirements of bone formation by osteoblasts, much less is known about the energetic requirements of bone resorption by osteoclasts. The abundance of mitochondria in mature osteoclasts suggests that the production of an acidified micro-environment conducive to the ionization of hydroxyapatite, secretion of matrix-degrading enzymes, and motility during resorption requires significant energetic capacity. To investigate the contribution of mitochondrial long chain fatty acid β-oxidation to osteoclast development, we disrupted the expression of carnitine palmitoyltransferase-2 (Cpt2) in myeloid-lineage cells. Fatty acid oxidation increases dramatically in bone marrow cultures stimulated with RANKL and M-CSF and microCT analysis revealed that the genetic inhibition of long chain fatty acid oxidation in osteoclasts significantly increases trabecular bone volume in female mice secondary to reduced osteoclast numbers. In line with these data, osteoclast precursors isolated from Cpt2 mutants exhibit reduced capacity to form large-multinucleated osteoclasts, which was not rescued by exogenous glucose or pyruvate, and signs of an energetic stress response. Together, our data demonstrate that mitochondrial long chain fatty acid oxidation by the osteoclast is required for normal bone resorption as its inhibition produces an intrinsic defect in osteoclast formation.
Elevation affects the ecological stoichiometry of Qinghai spruce in the Qilian Mountains of northwest China
Authors: Qin Huijun , Jiao Liang , Zhou Yi , Wu Jingjing , Che Xichen
Published: September 2022

Environmental heterogeneity in temperature, moisture, and soil fertility caused by elevation gradients can affect the trade-offs in the survival strategies of tree species. There is uncertainty about the allocation of resources to different tissues of trees in response to the elevation gradient with respect to carbon (C), nitrogen (N), and phosphorus (P). Here, the C, N, and P content of leaves, branches, trunks, and thick and fine roots of Picea crassifolia (Qinghai spruce) and their stoichiometric changes across three different elevations were investigated in the Qilian Mountains. We found that N:P of Qinghai spruce was <14 in all tissues at most elevations, indicating that Qinghai spruce was more susceptible to N limitation. Meanwhile, the N content and N:P of Qinghai spruce each were significantly negatively correlated with temperature (p < 0.05), and its P content was lower at high elevation. The contribution of soil–climate interactions on the elevation gradient to each tissue type was 34.02% (leaves), 16.84% (branches), 67.78% (trunks), 34.74% (thick roots), and 49.84% (fine roots), indicating that interacting climate and soil factors on the elevation gradient predominately drove the C, N, and P content and stoichiometry variation in each tissue type of Qinghai spruce trees. The results of this study clarify that the elevation gradient regulates the elemental content and resource allocation in Qinghai spruce, providing basic data and an important timely reference for future forest management in the regions where coniferous trees grows. These findings also help improve our understanding of elevational patterns of forest ecosystem stoichiometry in arid and semiarid regions.
Combined transcriptomic and proteomic analysis reveals multiple pathways involved in self-pollen tube development and the potential roles of FviYABBY1 in self-incompatibility in Fragaria viridis
Authors: Du Jianke , Ge Chunfeng , Wang Tao , Wang Jing , Ni Zhiyou , Xiao Shiwei , Zhao Fengli , Zhao Mizhen , Qiao Yushan
Published: September 2022

Fragaria viridis exhibits S-RNase-based gametophytic self-incompatibility, in which S-RNase is the major factor inhibiting pollen tube growth. However, the pathways involved in and the immediate causes of the inhibition of pollen tube growth remain unknown. Here, interactive RNA sequencing and proteome analysis revealed changes in the transcriptomic and proteomic profiles of F. viridis styles harvested at 0 and 24 h after self-pollination. A total of 2,181 differentially expressed genes and 200 differentially abundant proteins were identified during the pollen development stage of self-pollination. Differentially expressed genes and differentially abundant proteins associated with self-incompatible pollination were further mined, and multiple pathways were found to be involved. Interestingly, the expression pattern of the transcription factor FviYABBY1, which is linked to polar growth, differed from those of other genes within the same family. Specifically, FviYABBY1 expression was extremely high in pollen, and its expression trend in self-pollinated styles was consistent with that of S-RNase. Furthermore, FviYABBY1 interacted with S-RNase in a non-S haplotype way. Therefore, FviYABBY1 affects the expression of polar growth-related genes in self-pollen tubes and is positively regulated by S-RNase.