bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating immune complexes and mutations of HBsAg are associated with the undetectable HBsAg in anti-HBs and HBeAg positive occult hepatitis B virus infection
Authors: Yan Ying , Sun Huizhen , Chang Le , Ji Huimin , Jiang Xinyi , Song Shi , Xiao Yingzi , Feng Kaihao , Nuermaimaiti Abudulimutailipu , Lu Zhuoqun , Wang Lunan
Published: November 2022

Introduction

Occult hepatitis B virus infection (OBI) is an HBsAg negative state in HBV infection with usually inactive HBV replication. However, there were a minority of individuals with positive HBeAg and anti-HBs among OBI blood donors and few studies have focused on this unusual serological pattern.

Methods

2022 plasma of blood donors that preliminary screened reactive for HBV DNA and non-reactive for HBsAg were collected from 16 provinces in China from 2015 to 2018. HBV DNA and HBsAg in these samples were retested using the Cobas TaqScreen MPX test and ARCHITECT HBsAg Quantitative II assay. Lumipulse HBsAg-HQ assay and polyethylene glycol (PEG)-double precipitation following HCl and trypsin digestion were performed to detect HBsAg from HBsAg-anti-HBs circulating immune complexes (CICs).

Results

1487 of 2022 samples were positive for Cobas HBV DNA test and non-reactive for ARCHITECT HBsAg assay, while 404 of them were positive using Lumipulse HBsAg-HQ assay. 10 HBsAg-/anti-HBs+/HBeAg+ OBI blood donor samples were further dissociated and HBsAg-CICs were detected in 7 samples. Sequencing analysis showed that D44N, N98T, G73S, Del 56-116, and I161T occurred in the pre-S region, and immune escape mutations such as P127T, F134L, G145R, V168A, and I126T/S in the S region were found.

Discussion

In conclusion, there were a minority of HBsAg-/anti-HBs+/HBeAg+ individuals in OBI blood donors. The undetectable HBsAg in these individuals was mainly due to HBsAg-CICs. Immune escape-associated mutations also happened under the host’s selective pressure. HBsAg dissociation methods or Lumipulse HBsAg-HQ assay is recommended to distinguish these individuals.
Rapid, ultrasensitive, and highly specific identification of Brucella abortus utilizing multiple cross displacement amplification combined with a gold nanoparticles-based lateral flow biosensor
Authors: Yang Xinggui , Wang Yue , Liu Ying , Huang Junfei , Wei Xiaoyu , Tan Qinqin , Zeng Xiaoyan , Ying Xia , Li Shijun
Published: November 2022

Brucella abortus (B. abortus) as an important infectious agent of bovine brucellosis cannot be ignored, especially in countries/regions dominated by animal husbandry. Thus, the development of an ultrasensitive and highly specific identification technique is an ideal strategy to control the transmission of bovine brucellosis. In this report, a novel detection protocol, which utilizes multiple cross displacement amplification (MCDA) combined with a gold nanoparticles-based lateral flow biosensor (AuNPs-LFB) targeting the BruAb2_0168 gene was successfully devised and established for the identification of B. abortus (termed B. abortus-MCDA-LFB). Ten specific primers containing engineered C1-FAM (carboxyfluorescein) and D1-biotin primers were designed according to the MCDA reaction mechanism. These genomic DNA extracted from various bacterial strains and whole blood samples were used to optimize and evaluate the B. abortus-MCDA-LFB assay. As a result, the optimal reaction conditions for the B. abortus-MCDA-LFB assay were 66°C for 40 min. The limit of detection of the B. abortus-MCDA-LFB was 10 fg/μl (~3 copies/μl) for genomic DNA extracted from pure cultures of B. abortus isolate. Meanwhile, the B. abortus-MCDA-LFB assay accurately identified all tested B. abortus strains, and there was no cross-reaction with non-B. abortus pathogens. Moreover, the detection workflow of the B. abortus-MCDA-LFB assay for whole blood samples can be completed within 70 min, and the cost of a single test is approximately 5.0 USD. Taken together, the B. abortus-MCDA-LFB assay is a visual, fast, ultrasensitive, low-cost, easy-to-operate, and highly specific detection method, which can be used as a rapid identification tool for B. abortus infections.
Detoxification mechanisms of electroactive microorganisms under toxicity stress: A review
Authors: Feng Huajun , Xu Liyang , Chen Ruya , Ma Xiangjuan , Qiao Hua , Zhao Nannan , Ding Yangcheng , Wu Di
Published: November 2022

Remediation of environmental toxic pollutants has attracted extensive attention in recent years. Microbial bioremediation has been an important technology for removing toxic pollutants. However, microbial activity is also susceptible to toxicity stress in the process of intracellular detoxification, which significantly reduces microbial activity. Electroactive microorganisms (EAMs) can detoxify toxic pollutants extracellularly to a certain extent, which is related to their unique extracellular electron transfer (EET) function. In this review, the extracellular and intracellular aspects of the EAMs’ detoxification mechanisms are explored separately. Additionally, various strategies for enhancing the effect of extracellular detoxification are discussed. Finally, future research directions are proposed based on the bottlenecks encountered in the current studies. This review can contribute to the development of toxic pollutants remediation technologies based on EAMs, and provide theoretical and technical support for future practical engineering applications.
A new order, Entrophosporales, and three new Entrophospora species in Glomeromycota
Authors: Błaszkowski Janusz , Sánchez-García Marisol , Niezgoda Piotr , Zubek Szymon , Fernández Félix , Vila Ana , Al-Yahya’ei Mohamed N. , Symanczik Sarah , Milczarski Paweł , Malinowski Ryszard , Cabello Marta , Goto Bruno Tomio , Casieri Leonardo , Malicka Monika , Bierza Wojciech , Magurno Franco
Published: November 2022

As a result of phylogenomic, phylogenetic, and morphological analyses of members of the genus Claroideoglomus, four potential new glomoid spore-producing species and Entrophospora infrequens, a new order, Entrophosporales, with one family, Entrophosporaceae (=Claroideoglomeraceae), was erected in the phylum Glomeromycota. The phylogenomic analyses recovered the Entrophosporales as sister to a clade formed by Diversisporales and Glomeraceae. The strongly conserved entrophosporoid morph of E. infrequens, provided with a newly designated epitype, was shown to represent a group of cryptic species with the potential to produce different glomoid morphs. Of the four potential new species, three enriched the Entrophosporales as new Entrophospora species, E. argentinensis, E. glacialis, and E. furrazolae, which originated from Argentina, Sweden, Oman, and Poland. The fourth fungus appeared to be a glomoid morph of the E. infrequens epitype. The physical association of the E. infrequens entrophosporoid and glomoid morphs was reported and illustrated here for the first time. The phylogenetic analyses, using nuc rDNA and rpb1 concatenated sequences, confirmed the previous conclusion that the genus Albahypha in the family Entrophosporaceae sensu Oehl et al. is an unsupported taxon. Finally, the descriptions of the Glomerales, Entrophosporaceae, and Entrophospora were emended and new nomenclatural combinations were introduced.
The effect of tuina on ulcerative colitis model mice analyzed by gut microbiota and proteomics
Authors: Wang Hourong , Liu Zhifeng , Yu Tianyuan , Zhang Yingqi , Jiao Yi , Wang Xiangyi , Du Hongjin , Jiang Ruichen , Liu Di , Xu Yajing , Guan Qian , Lu Mengqian
Published: November 2022

Tuina can effectively alleviate ulcerative colitis-related symptoms, but the mechanism of action is unknown. The purpose of this research is to explore potential pathways for the treatment of tuina through gut microbiota and proteomics techniques. Thirty-two male BALB/c mice were divided into four groups, the control, model, mesalazine, and tuina groups. The ulcerative colitis model was established by freely drinking a 3% dextran sulphate sodium solution for 7 days. The mesalazine group and the tuina group, respectively, received 7 days of mesalazine and tuina treatment. Subsequently, their body weights, feces properties, colon length, histomorphological changes, gut microbiota, and colon proteomics were determined. Body weights, disease activity index score, colon histological scores, and microbiota diversity were restored in the tuina group. At the phylum level, Firmicutes was increased and Bacteroidota decreased. At the family level, Lachnospiraceae increased and Prevotellaceae decreased. At the genus level, the Lachnospiraceae_NK4A136_group was increased. Proteomics detected 370 differentially expressed proteins regulated by tuina, enriched to a total of 304 pathways, including biotin metabolism, Notch signaling pathway, linoleic acid metabolism, and autophagy. Tuina can effectively improve the symptoms of weight loss, fecal properties, and colon inflammation in ulcerative colitis mice and restore the gut microbiota diversity, adjusting the relative abundance of microbiota. The therapeutic effects of tuina may be achieved by modulating the signaling pathways of biotin metabolism, Notch signaling pathway, linoleic acid metabolism, and autophagy.
Survival, metabolic activity, and ultrastructural damages of Antarctic black fungus in perchlorates media
Authors: Cassaro Alessia , Pacelli Claudia , Onofri Silvano
Published: November 2022

Evidence from recent Mars landers identified the presence of perchlorates salts at 1 wt % in regolith and their widespread distribution on the Martian surface that has been hypothesized as a critical chemical hazard for putative life forms. However, the hypersaline environment may also potentially preserve life and its biomolecules over geological timescales. The high concentration of natural perchlorates is scarcely reported on Earth. The presence of perchlorates in soil and ice has been recorded in some extreme environments including the McMurdo Dry Valleys in Antarctica, one of the best terrestrial analogues for Mars. In the frame of “Life in space” Italian astrobiology project, the polyextremophilic black fungus Cryomyces antarcticus, a eukaryotic test organism isolated from the Antarctic cryptoendolithic communities, has been tested for its resistance, when grown on different hypersaline substrata. In addition, C. antarcticus was grown on Martian relevant perchlorate medium (0.4 wt% of Mg(ClO4)2 and 0.6 wt% of Ca(ClO4)2) to investigate the possibility for the fungus to survive in Martian environment. Here, the results indicate a good survivability and metabolic activity recovery of the black fungus when grown on four Martian relevant perchlorates. A low percentage of damaged cellular membranes have been found, confirming the ultrastructural investigation.
Caspase-1 and the inflammasome promote polycystic kidney disease progression
Authors: Swenson-Fields Katherine I. , Ward Christopher J. , Lopez Micaila E. , Fross Shaneann , Heimes Dillon Anna L. , Meisenheimer James D. , Rabbani Adib J. , Wedlock Emily , Basu Malay K. , Jansson Kyle P. , Rowe Peter S. , Stubbs Jason R. , Wallace Darren P. , Vitek Michael P. , Fields Timothy A.
Published: November 2022

We and others have previously shown that the presence of renal innate immune cells can promote polycystic kidney disease (PKD) progression. In this study, we examined the influence of the inflammasome, a key part of the innate immune system, on PKD. The inflammasome is a system of molecular sensors, receptors, and scaffolds that responds to stimuli like cellular damage or microbes by activating Caspase-1, and generating critical mediators of the inflammatory milieu, including IL-1β and IL-18. We provide evidence that the inflammasome is primed in PKD, as multiple inflammasome sensors were upregulated in cystic kidneys from human ADPKD patients, as well as in kidneys from both orthologous (PKD1RC/RC or RC/RC) and non-orthologous (jck) mouse models of PKD. Further, we demonstrate that the inflammasome is activated in female RC/RC mice kidneys, and this activation occurs in renal leukocytes, primarily in CD11c+ cells. Knock-out of Casp1, the gene encoding Caspase-1, in the RC/RC mice significantly restrained cystic disease progression in female mice, implying sex-specific differences in the renal immune environment. RNAseq analysis implicated the promotion of MYC/YAP pathways as a mechanism underlying the pro-cystic effects of the Caspase-1/inflammasome in females. Finally, treatment of RC/RC mice with hydroxychloroquine, a widely used immunomodulatory drug that has been shown to inhibit the inflammasome, protected renal function specifically in females and restrained cyst enlargement in both male and female RC/RC mice. Collectively, these results provide evidence for the first time that the activated Caspase-1/inflammasome promotes cyst expansion and disease progression in PKD, particularly in females. Moreover, the data suggest that this innate immune pathway may be a relevant target for therapy in PKD.
Analysis of shared underlying mechanism in neurodegenerative disease
Authors: Butler Rickeem , Bradford David , Rodgers Kathleen E.
Published: November 2022

In this review, the relationship between bioenergetics, mitochondrial dysfunction, and inflammation will be and how they contribute to neurodegeneration, specifically in Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) will be reviewed. Long-term changes in mitochondrial function, autophagy dysfunction, and immune activation are commonalities shared across these age-related disorders. Genetic risk factors for these diseases support an autophagy-immune connection in the underlying pathophysiology. Critical areas of deeper evaluation in these bioenergetic processes may lead to potential therapeutics with efficacy across multiple neurodegenerative diseases.
New models of Parkinson’s like neuroinflammation in human microglia clone 3: Activation profiles induced by INF-γ plus high glucose and mitochondrial inhibitors
Authors: De Chirico Francesca , Poeta Eleonora , Babini Giorgia , Piccolino Iliana , Monti Barbara , Massenzio Francesca
Published: November 2022

Microglia activation and neuroinflammation have been extensively studied in murine models of neurodegenerative diseases; however, to overcome the genetic differences between species, a human cell model of microglia able to recapitulate the activation profiles described in patients is needed. Here we developed human models of Parkinson’s like neuroinflammation by using the human microglia clone 3 (HMC3) cells, whose activation profile in response to classic inflammatory stimuli has been controversial and reported only at mRNA levels so far. In fact, we showed the increased expression of the pro-inflammatory markers iNOS, Caspase 1, IL-1β, in response to IFN-γ plus high glucose, a non-specific disease stimulus that emphasized the dynamic polarization and heterogenicity of the microglial population. More specifically, we demonstrated the polarization of HMC3 cells through the upregulation of iNOS expression and nitrite production in response to the Parkinson’s like stimuli, 6-hydroxidopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the latter depending on the NF-κB pathway. Furthermore, we identified inflammatory mediators that promote the pro-inflammatory activation of human microglia as function of different pathways that can simulate the phenotypic transition according to the stage of the pathology. In conclusion, we established and characterized different systems of HMC3 cells activation as in vitro models of Parkinson’s like neuroinflammation.
Assessment of human expertise and movement kinematics in first-person shooter games
Authors: Donovan Ian , Saul Marcia A. , DeSimone Kevin , Listman Jennifer B. , Mackey Wayne E. , Heeger David J.
Published: November 2022

In contrast to traditional professional sports, there are few standardized metrics in professional esports (competitive multiplayer video games) for assessing a player's skill and ability. We assessed the performance of professional-level players in Aim LabTM, a first-person shooter training and assessment game, with two target-shooting tasks. These tasks differed primarily in target size: the task with large targets provided an incentive to be fast but imprecise and the task with large targets provided an incentive to be precise but slow. Each player's motor acuity was measured by characterizing the speed-accuracy trade-off in shot behavior: shot time (elapsed time for a player to shoot at a target) and shot spatial error (distance from center of a target). We also characterized the fine-grained kinematics of players' mouse movements. Our findings demonstrate that: 1) movement kinematics depended on task demands; 2) individual differences in motor acuity were significantly correlated with kinematics; and 3) performance, combined across the two target sizes, was poorly characterized by Fitts Law. Our approach to measuring motor acuity has widespread applications not only in esports assessment and training, but also in basic (motor psychophysics) and clinical (gamified rehabilitation) research.
Detection of differentially expressed genes in spatial transcriptomics data by spatial analysis of spatial transcriptomics: A novel method based on spatial statistics
Authors: Qiu Zhihua , Li Shaojun , Luo Ming , Zhu Shuanggen , Wang Zhijian , Jiang Yongjun
Published: November 2022

Background

Spatial transcriptomics (STs) simultaneously obtains the location and amount of gene expression within a tissue section. However, current methods like FindMarkers calculated the differentially expressed genes (DEGs) based on the classical statistics, which should abolish the spatial information.

Materials and methods

A new method named spatial analysis of spatial transcriptomics (saSpatial) was developed for both the location and the amount of gene expression. Then saSpatial was applied to detect DEGs in both inter- and intra-cross sections. DEGs detected by saSpatial were compared with those detected by FindMarkers.

Results

Spatial analysis of spatial transcriptomics was founded on the basis of spatial statistics. It was able to detect DEGs in different regions in the normal brain section. As for the brain with ischemic stroke, saSpatial revealed the DEGs for the ischemic core and penumbra. In addition, saSpatial characterized the genetic heterogeneity in the normal and ischemic cortex. Compared to FindMarkers, a larger number of valuable DEGs were found by saSpatial.

Conclusion

Spatial analysis of spatial transcriptomics was able to effectively detect DEGs in STs data. It was a simple and valuable tool that could help potential researchers to find more valuable genes in the future research.
Valproic acid exposure decreases neurogenic potential of outer radial glia in human brain organoids
Authors: Zang Zhenle , Yin Huachun , Du Zhulin , Xie Ruxin , Yang Ling , Cai Yun , Wang Liuyongwei , Zhang Dandan , Li Xin , Liu Tianyao , Gong Hong , Gao Junwei , Yang Hui , Warner Margaret , Gustafsson Jan-Ake , Xu Haiwei , Fan Xiaotang
Published: November 2022

Valproic acid (VPA) exposure during pregnancy leads to a higher risk of autism spectrum disorder (ASD) susceptibility in offspring. Human dorsal forebrain organoids were used to recapitulate course of cortical neurogenesis in the developing human brain. Combining morphological characterization with massive parallel RNA sequencing (RNA-seq) on organoids to analyze the pathogenic effects caused by VPA exposure and critical signaling pathway. We found that VPA exposure in organoids caused a reduction in the size and impairment in the proliferation and expansion of neural progenitor cells (NPCs) in a dose-dependent manner. VPA exposure typically decreased the production of outer radial glia-like cells (oRGs), a subtype of NPCs contributing to mammalian neocortical expansion and delayed their fate toward upper-layer neurons. Transcriptomics analysis revealed that VPA exposure influenced ASD risk gene expression in organoids, which markedly overlapped with irregulated genes in brains or organoids originating from ASD patients. We also identified that VPA-mediated Wnt/β-catenin signaling pathway activation is essential for sustaining cortical neurogenesis and oRGs output. Taken together, our study establishes the use of dorsal forebrain organoids as an effective platform for modeling VPA-induced teratogenic pathways involved in the cortical neurogenesis and oRGs output, which might contribute to ASD pathogenesis in the developing brain.
Valorization of jackfruit waste into value added products and their potential applications
Authors: Pathak Neelam , Singh Sangram , Singh Pankaj , Singh Pradeep Kumar , Singh Ranjan , Bala Saroj , Thirumalesh Banjagere Veerabhadrappa , Gaur Rajeeva , Tripathi Manikant
Published: November 2022

Jackfruit is a potential natural resource for many valuable biomaterials. The wastes from jackfruit are rich in carbohydrate, proteins, fats and phytochemicals. These wastes can be used as feedstock for the development of various bioproducts. The pretreatment strategies like biological, physical and chemical methods are being used for effective valorization of fruit wastes into value added products, like bioethanol, biogas, bioplastics, feeds, functional food additives, and other useful compounds. Bioenergy production from such renewable resources is an eco-friendly and cost-effective alternative option of fuels, unlike fossil fuels. The efficient bioconversion of fruit waste into useful biomaterials is facilitated by microbial fermentation process. Also, jackfruit peel is applied in the pollution abatement by remediation of dyes color from contaminated aquatic environment. Such technology can be used to develop a green economic model for waste utilization. This review addressed the utilization feasibility of jackfruit waste to produce value added products in order to reduce wastes and protect environment in a sustainable way.
Changes in body composition during the macrocycle of professional football players in relation to sports nutrition knowledge
Authors: Staśkiewicz Wiktoria , Grochowska-Niedworok Elzbieta , Zydek Grzegorz , Białek-Dratwa Agnieszka , Grajek Mateusz , Jaruga-Sȩkowska Sylwia , Kowalski Oskar , Kardas Marek
Published: November 2022

Professional football players are obligated to meet the physical demands and maintain the best possible performance throughout the whole macrocycle. It is important to assess the players' nutrition knowledge, identify areas that require increased nutrition awareness and identify the impact of knowledge on changes in body composition as this can affect the players' health and performance. This study aimed to assess changes in the body composition of professional football players during the macrocycle of the spring round of the football championship and to identify the correlation between nutrition knowledge and maintaining body composition. The study included 38 football players. The players' body compositions were analyzed 6 times during the macrocycle consisting of preparatory, competitive, and transition periods using the Direct Segmental Multi-Frequency Bioelectrical Impedance Analysis method. Athletes completed the Nutrition for Sport Knowledge Questionnaire to assess their nutrition knowledge. During the preparatory period, a statistically significant negative correlation was demonstrated between the players' knowledge about the subsections of micronutrients in the diet and the dispersion of the adipose percentage tissue content (r= −0.36,p= 0.03). In the competitive period, there was a statistically significant negative correlation between the players' knowledge of sports nutrition and the dispersion of lean body mass (r= −0.46,p= 0.004), and skeletal muscle mass (r= −0.36,p= 0.03). During the transition period, a statistically significant negative correlation between the players' knowledge of weight control and the dispersion of body mass (r= −0.47,p= 0.00) and BMI values (r= −0.48,p= 0.00) was identified. The player's knowledge about the subsection of macronutrients significantly negatively correlated with the dispersion of skeletal muscle mass content (r= −0.33,p= 0.05). Nutrition knowledge has an impact on the stability of body composition during all analyzed periods: preparatory, competitive, and transition periods.
Case report: Spontaneous remission of synchronous endometrial and ovarian cancers following pregnancy
Authors: Daley Diandra , Padwick Malcolm , Mistry Sabina , Malhotra Vivek , Vikram Radhika Selvi , Stanciu Paul
Published: November 2022

Introduction

Endometrial cancer is one of the most common malignancies affecting women. It is uncommonly diagnosed in young women, particularly in the absence of abnormal vaginal bleeding symptoms.

Case presentation

A 28-year-old woman was referred to our department with lower abdominal pain. Transvaginal ultrasound showed a complex right adnexal mass with mixed echogenicity. Magnetic resonance imaging (MRI) identified a right-sided, torted, cystic solid ovarian mass, and a polypoid lesion in the uterine cavity.

Diagnosis

Following multidisciplinary team advice, hysteroscopic transcervical resection of endometrial polypoid mass and laparoscopic right salpingo-oophorectomy was performed. Histopathologic assessment of the endometrial tissue showed changes consistent with grade 1 endometrioid endometrial carcinoma, while the right ovarian mass showed a well-differentiated endometrioid carcinoma.

Intervention

The patient underwent hormonal treatment and surveillance whilst making a final decision regarding further surgical management. However, the patient stopped hormonal treatment after 2 weeks, went abroad and absconded from treatment for 8 months. On her return, she had conceived naturally and was in the first trimester of pregnancy. Further management was postponed until the patient was 7 weeks postnatal. The patient was not keen on any further surgical management and opted for close surveillance with ultrasound scans and hysteroscopies with endometrial biopsies. All subsequent endometrial biopsies showed normal endometrium, with no evidence of hyperplasia or malignancy.

Outcome

To date, the patient remains on a 6-monthly surveillance plan and is considered to have had complete natural remission of her endometrial and ovarian cancers following pregnancy.

Conclusion

This unique case demonstrates a natural phenomenon, in which the complete, natural remission of endometrial and ovarian cancers occurred following pregnancy and childbirth. The aetiology may be related to the high progesterone levels occurring in pregnancy.
Intratumoral microbiome and gastrointestinal cancers
Authors: Li Shengnan , Li Qian , Lu Wei
Published: November 2022

Emerging studies have revealed the role of microbiota in regulating tumorigenesis, development, and response to antitumor treatment. However, most studies have focused on gut microbiota, and little is known about the intratumoral microbiome. To date, the latest research has indicated that the intratumoral microbiome is a key component of the tumor microenvironment (TME), and can promote a heterogeneous immune microenvironment, reprogram tumor metabolism to affect tumor invasion and metastasis. In this review, we will summarize existing studies on the intratumoral microbiome of gastrointestinal cancers and reveal their crosstalk. This will provide a better understanding of this emerging field and help to explore new therapeutic approaches for cancer patients by targeting the intratumoral microbiome.
Histone acetylation modifications: A potential targets for the diagnosis and treatment of papillary thyroid cancer
Authors: Chen Chongyang , Liu Jingfang
Published: November 2022

Thyroid cancer is a common malignancy of the endocrine system, with papillary thyroid cancer (PTC) being the most common type of pathology. The incidence of PTC is increasing every year. Histone acetylation modification is an important part of epigenetics, regulating histone acetylation levels through histone acetylases and histone deacetylases, which alters the proliferation and differentiation of PTC cells and affects the treatment and prognosis of PTC patients. Histone deacetylase inhibitors induce histone acetylation, resulting in the relaxation of chromatin structure and activation of gene transcription, thereby promoting differentiation, apoptosis, and growth arrest of PTC cells.
Management of infantile hemangiomas: Recent advances
Authors: Xu Wei , Zhao Haiguang
Published: November 2022

Infantile hemangiomas (IHs) are benign vascular tumors commonly observed in children. A small number of cases can manifest as organ or system dysfunction, permanent scarring, or even disfigurement. Currently, diagnosis is mainly based on clinical history, physical examination, and auxiliary inspection. In the treatment of a hemangioma, the functional damage caused by the lesion and complications that may endanger the patient’s life should be given priority. This suggests that identification, diagnosis, and referral to specialists during the early stages of IHs are important factors in preventing related complications and obtaining a better prognosis. During the past few decades, researchers have explored different treatments according to the condition, including oral or topical drugs, topical drug injections, laser surgery, and surgical treatment. However, oral propranolol remains a well-accepted first-line treatment. This article will primarily focus on the recent advances in the clinical diagnosis and treatment of hemangiomas, along with a literature review on the subject.
Chimeric antigen receptor T-cell therapy for T-ALL and AML
Authors: Wei Wenwen , Yang Dong , Chen Xi , Liang Dandan , Zou Liqun , Zhao Xudong
Published: November 2022

Non-B-cell acute leukemia is a term that encompasses T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML). Currently, the therapeutic effectiveness of existing treatments for refractory or relapsed (R/R) non-B-cell acute leukemia is limited. In such situations, chimeric antigen receptor (CAR)-T cell therapy may be a promising approach to treat non-B-cell acute leukemia, given its promising results in B-cell acute lymphoblastic leukemia (B-ALL). Nevertheless, fratricide, malignant contamination, T cell aplasia for T-ALL, and specific antigen selection and complex microenvironment for AML remain significant challenges in the implementation of CAR-T therapy for T-ALL and AML patients in the clinic. Therefore, designs of CAR-T cells targeting CD5 and CD7 for T-ALL and CD123, CD33, and CLL1 for AML show promising efficacy and safety profiles in clinical trials. In this review, we summarize the characteristics of non-B-cell acute leukemia, the development of CARs, the CAR targets, and their efficacy for treating non-B-cell acute leukemia.
Case Report: Anal canal duplication associated with anorectal stenosis—A rare presentation
Authors: Zheng Zhen , Xiao Dong , Wang Junxiang , Xu Haozhong , Mao Jianxiong , Wang Xiuliang
Published: November 2022

Anal canal duplication is a rare gastrointestinal malformation characterized by extra anal orifices at 6 o'clock in the lithotomy position. To date, there have been only 110 reported cases. The purpose of this study is to contribute two infant cases, one of which is associated with anorectal stenosis, which has never been described.
Noble gas and neuroprotection: From bench to bedside
Authors: Yin Haiying , Chen Zijun , Zhao Hailin , Huang Han , Liu Wenwen
Published: November 2022

In recent years, inert gases such as helium, argon, and xenon have gained considerable attention for their medical value. Noble gases present an intriguing scientific paradox: although extremely chemically inert, they display a remarkable spectrum of clinically useful biological properties. Despite a relative paucity of knowledge about their mechanisms of action, some noble gases have been used successfully in clinical practice. The neuroprotection elicited by these noble gases has been investigated in experimental animal models of various types of brain injuries, such as traumatic brain injury, stroke, subarachnoid hemorrhage, cerebral ischemic/reperfusion injury, and neurodegenerative diseases. Collectively, these central nervous system injuries are a leading cause of morbidity and mortality every year worldwide. Treatment options are presently limited to thrombolytic drugs and clot removal for ischemic stroke, or therapeutic cooling for other brain injuries before the application of noble gas. Currently, there is increasing interest in noble gases as novel treatments for various brain injuries. In recent years, neuroprotection elicited by particular noble gases, xenon, for example, has been reported under different conditions. In this article, we have reviewed the latest in vitro and in vivo experimental and clinical studies of the actions of xenon, argon, and helium, and discuss their potential use as neuroprotective agents.
LncRNA MEG3: Potential stock for precision treatment of cardiovascular diseases
Authors: Li Zining , Gao Jialiang , Sun Di , Jiao Qian , Ma Jing , Cui Weilu , Lou Yuqing , Xu Fan , Li Shanshan , Li Haixia
Published: November 2022

The prevalence and mortality rates of cardiovascular diseases are increasing, and new treatment strategies are urgently needed. From the perspective of basic pathogenesis, the occurrence and development of cardiovascular diseases are related to inflammation, apoptosis, fibrosis and autophagy of cardiomyocytes, endothelial cells and other related cells. The involvement of maternally expressed gene 3 (MEG3) in human disease processes has been increasingly reported. P53 and PI3K/Akt are important pathways by which MEG3 participates in regulating cell apoptosis. MEG3 directly or competitively binds with miRNA to participate in apoptosis, inflammation, oxidative stress, endoplasmic reticulum stress, EMT and other processes. LncRNA MEG3 is mainly involved in malignant tumors, metabolic diseases, immune system diseases, cardiovascular and cerebrovascular diseases, etc., LncRNA MEG3 has a variety of pathological effects in cardiomyocytes, fibroblasts and endothelial cells and has great clinical application potential in the prevention and treatment of AS, MIRI, hypertension and HF. This paper will review the research progress of MEG3 in the aspects of mechanism of action, other systemic diseases and cardiovascular diseases, and point out its great potential in the prevention and treatment of cardiovascular diseases. lncRNAs also play a role in endothelial cells. In addition, lncRNA MEG3 has shown biomarker value, prognostic value and therapeutic response measurement in tumor diseases. We boldly speculate that MEG3 will play a role in the emerging discipline of tumor heart disease.
Intra-articular injection of placental mesenchymal stromal cells ameliorates pain and cartilage anabolism/catabolism in knee osteoarthritis
Authors: Fan Mengqiang , Zhang Jingwen , Zhou Li , Chen Zuxiang , Bao Ronghua , Zheng Longpo , Tong Peijian , Ma Yuhai , Shan Letian
Published: November 2022

Background: Knee Osteoarthritis (kOA), the most common joint degenerative disorder, lacks effective therapeutics. Placenta-derived mesenchymal stromal cells (PMSCs) are effective in tissue repairing and generation, which have potential in treating kOA. This study aimed to determine the anti-kOA efficacy of PMSCs and to explore its action mode.

Methods: Flow cytometry and three-line differentiation were performed for identification of PMSCs. In vivo, a rat kOA model established by anterior cruciate ligament transection (ACLT) surgery was used to evaluate the efficacy of PMSCs. Histopathological HE and SO staining with Osteoarthritis Research Society International scoring were conducted, and cartilage expressions of MMP13 and Col2 were measured by immunohistochemistry. Pain behavior parameters by mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL), were measured. In vitro, wound healing and cell immunofluorescence assays were conducted to detect the proliferation and migration ability of chondrocytes treated with PMSCs conditioned medium (PMSCs-CM). Quantitative real-time PCR (qRT-PCR) and Western blot (WB) assays were applied to explore the molecular action of PMSCs on chondrocytes.

Results: The results of flow cytometry indicated that the surface markers of PMSCs (CD73 > 95%, CD90 > 95%, and CD34 < 2%) were consistent with the typical mesenchymal stromal cells. The in vivo data showed that PMSCs significantly reversed the kOA progression by protection of cartilage, regulation of anabolic (Col2) and catabolic (MMP13) expressions, and relief of pain symptoms. The in vitro data showed that PMSCs promoted chondrocyte proliferation and migration and significantly restored the IL-1β-induced abnormal gene expressions of Col2, Mmp13, Adamts4, Adamts5 and Sox9 and also restored the abnormal protein expressions of Col2, Mmp13 and Sox9 of chondrocytes. The molecular actions of PMSCs on chondrocytes in nested co-culture way or in conditioned medium way were similar, confirming a paracrine-based mode of action.

Conclusion: This study demonstrated PMSCs’ anti-kOA efficacy and its paracrine-based action mode, providing novel knowledge of PMSCs and suggesting it as a promising cell therapy for treatment of kOA.
Adjuvant effects of Chinese medicinal tonics on gastric, liver, and colorectal cancers—OMICs-based contributions to understanding their mechanism of action
Authors: Zuo Zhigang , Jia Jia , Li Hongliang , Shi Run , Wang Di , Zeng Ke-Wu , Nie Hong , Wang Xin-Guo , Liu Wen , Li Minglun , Feng Yibin , Wang Xuan Bin
Published: November 2022

Gastric, liver, and colorectal cancers belong to gastrointestinal (GI) cancers, one of the most threatening diseases in the world. The tonics class in Chinese medicines plays a critical role in antigastrointestinal cancer as adjuvants. However, it is a challenge to study the effects and underlying mechanisms of tonics due to their multiple components and multiple targets; OMICs were introduced to facilitate the investigation of the complex mixture of tonics. In this review, the online databases PubMed, ProQuest, Web of Knowledge, China National Knowledge Infrastructure (CNKI), Chongqing VIP, and Wanfang were retrieved from 1 January 2011 to 31 May 2022, in an aim to summarize and discuss the research progress of the effects and, especially, the underlying mechanisms of tonics for antigastrointestinal cancers via OMICs. The results showed that through the combination of OMICs and other technologies, tonics have been used for gastrointestinal cancer by targeting cancer hallmarks, enhancing body resistance to carcinogenesis, enhancing therapeutic effects, and/or decreasing side effects. In conclusion, tonics may play a promising role in gastric, liver, and colorectal cancers as adjuvants and can be well investigated via the combination of OMICs and other technologies, which deserves further study.
Antiviral effects of the petroleum ether extract of Tournefortia sibirica L. against enterovirus 71 infection in vitro and in vivo
Authors: Huang Xinyu , Li Jiemin , Hong Yan , Jiang Chenghan , Wu Jiaxin , Wu Min , Sheng Rui , Liu Hongtao , Sun Jie , Xin Ying , Su Weiheng
Published: November 2022

Enterovirus 71 (EV71) is the major cause of severe hand, foot, and mouth disease (HFMD). Compared to other HFMD pathogens, like coxsackievirus A16 (CVA16), EV71 can invade the central nervous system and cause permanent damage. At present, there are no available antivirals against EV71 for clinical treatment. Herein, multiple Chinese botanical drugs were collected, and 47 types of botanical extracts were extracted using aqueous solutions and organic solvents. Based on the cytopathic effect inhibition assay, petroleum ether extract of Tournefortia sibirica L. (PE-TS) demonstrated 97.25% and 94.75% inhibition rates for EV71 infection (at 250 μg/ml) and CVA16 infection (at 125 μg/ml), respectively, with low cytotoxicity. Preliminary mechanistic studies showed that PE-TS inhibits replication of EV71 genomic RNA and synthesis of the EV71 protein. The released extracellular EV71 progeny virus titer decreased by 3.75 lg under PE-TS treatment. Furthermore, using a newborn mouse model, PE-TS treatment protected 70% and 66.7% of mice from lethal dose EV71 intracranial challenge via administration of intraperitoneal injection at 0.4 mg/g and direct lavage at 0.8 mg/g, respectively. The chemical constituents of the PE-TS were analyzed by Gas Chromatography-Mass Spectrometer (GC-MS), and a total of 60 compounds were identified. Compound-target network analysis and molecular docking implied potential bioactive compounds and their protein targets against EV71 associated pathology. The present study identified antiviral effects of PE-TS against EV71/CVA16 infection in vitro and EV71 infection in vivo, providing a potential antiviral botanical drug extract candidate for HFMD drug development.
Evaluation of the transverse aortic constriction model in ICR and C57BL/6J mice
Authors: Huang Mengying , Yu Lishuang , Wang Xiaoping , Wang Mingmin , Li Weili , Tang Jiayang , Ling Guanjing , Wei Xiaoqi , Wang Yong , Wang Wei , Wu Yan , Lu Linghui
Published: November 2022

Transverse aortic constriction (TAC) is a frequently used model to investigate pressure overload-induced progressive heart failure (HF); however, there is considerable phenotypic variation among different mouse strains and even sub-strains. Moreover, less is known about the TAC model in ICR mice. Therefore, to determine the suitability of the ICR strain for TAC-induced HF research, we compared the effects of TAC on ICR and C57BL/6J mice at one, two and four weeks post-TAC via echocardiography, organ index, morphology, and histology. At the end of the study, behavior and gene expression patterns were assessed, and overall survival was monitored. Compared to the sham-operated mice, ICR and C57BL/6J mice displayed hypertrophic phenotypes with a significant increase in ventricle wall thickness, heart weight and ratio, and cross-sectional area of cardiomyocytes after a 2-week TAC exposure. In addition, ICR mice developed reduced systolic function and severe lung congestion 4 weeks post-TAC, whereas C57BL/6J did not. Besides, ICR mice demonstrated comparable survival, similar gene expression alteration but severer fibrotic remodeling and poor behavioral performance compared to the C57BL/6J mice. Our data demonstrated that ICR was quite sensitive to TAC-induced heart failure and can be an ideal research tool to investigate mechanisms and drug intervention for pressure overload-induced HF.
Transcription factor GATA6 promotes migration of human coronary artery smooth muscle cells in vitro
Authors: Alajbegovic Azra , Daoud Fatima , Ali Neserin , Kawka Katarzyna , Holmberg Johan , Albinsson Sebastian
Published: November 2022

Vascular smooth muscle cell plasticity plays a pivotal role in the pathophysiology of vascular diseases. Despite compelling evidence demonstrating the importance of transcription factor GATA6 in vascular smooth muscle, the functional role of GATA6 remains poorly understood. The aim of this study was to elucidate the role of GATA6 on cell migration and to gain insight into GATA6-sensitive genes in smooth muscle. We found that overexpression of GATA6 promotes migration of human coronary artery smooth muscle cells in vitro, and that silencing of GATA6 in smooth muscle cells resulted in reduced cellular motility. Furthermore, a complete microarray screen of GATA6-sensitive gene transcription resulted in 739 upregulated and 248 downregulated genes. Pathways enrichment analysis showed involvement of transforming growth factor beta (TGF-β) signaling which was validated by measuring mRNA expression level of several members. Furthermore, master regulators prediction based on microarray data revealed several members of (mitogen activated protein kinase) MAPK pathway as a master regulators, reflecting involvement of MAPK pathway also. Our findings provide further insights into the functional role of GATA6 in vascular smooth muscle and suggest that targeting GATA6 may constitute as a new approach to inhibit vascular smooth muscle migration.
Commentary: Constipation caused by anti-calcitonin gene-related peptide migraine therapeutics explained by antagonism of calcitonin gene-related peptide’s motor-stimulating and prosecretory function in the intestine
Authors: Mackenzie Kimberly D. , Ortega Mario , Kessler Yoel , Campos Verena Ramirez , Krasenbaum Lynda J. , Carr Karen , Ning Xiaoping , Stratton Jennifer
Published: November 2022

Calcitonin gene-related peptide (CGRP) pathway-targeted treatments have been shown to be efficacious in the prevention of episodic and chronic migraine. Currently approved therapies include monoclonal antibodies (mAbs) that target CGRP (eptinezumab, fremanezumab, and galcanezumab) and the CGRP receptor (erenumab), and small molecule CGRP receptor antagonists (atogepant and rimegepant). While CGRP pathway–targeted treatments are generally well-tolerated, in a review article by Holzer and Holzer-Petsche published in the January 2022 issue of Frontiers in Physiology the authors discussed the role of the CGRP pathway in gastrointestinal physiology, with a specific focus on constipation associated with the use of CGRP pathway–targeted treatments. The authors state that real-world surveys have shown constipation to be a “major adverse event” reported in “more than 50% of patients treated with erenumab, fremanezumab or galcanezumab.” As described in the current commentary, the limited data from the cited references in the review article by Holzer and Holzer-Petsche do not support that statement.
Study on potential markers for diagnosis of renal cell carcinoma by serum untargeted metabolomics based on UPLC-MS/MS
Authors: Wang Jun , Yang Wen-Yu , Li Xiao-Han , Xu Bei , Yang Yu-Wei , Zhang Bin , Dai Chun-Mei , Feng Jia-Fu
Published: November 2022

Objective: Renal cell carcinoma (RCC) is the most common malignancy of the kidney. However, there is no reliable biomarker with high sensitivity and specificity for diagnosis and differential diagnosis. This study aims to analyze serum metabolite profile of patients with RCC and screen for potential diagnostic biomarkers.

Methods: Forty-five healthy controls (HC), 40 patients with benign kidney tumor (BKT) and 46 patients with RCC were enrolled in this study. Serum metabolites were detected by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and then subjected to multivariate statistical analysis, metabolic pathway analysis and diagnostic performance evaluation.

Results: The changes of glycerophospholipid metabolism, phosphatidylinositol signaling system, glycerolipid metabolism, d-glutamine and d-glutamate metabolism, galactose metabolism, and folate biosynthesis were observed in RCC group. Two hundred and forty differential metabolites were screened between RCC and HC groups, and 64 differential metabolites were screened between RCC and BKT groups. Among them, 4 differential metabolites, including 3-β-D-Galactosyl-sn-glycerol, 7,8-Dihydroneopterin, lysophosphatidylcholine (LPC) 19:2, and γ-Aminobutyryl-lysine (an amino acid metabolite), were of high clinical value not only in the diagnosis of RCC (RCC group vs. HC group; AUC = 0.990, 0.916, 0.909, and 0.962; Sensitivity = 97.73%, 97.73%, 93.18%, and 86.36%; Specificity = 100.00%, 73.33%, 80.00%, and 95.56%), but also in the differential diagnosis of benign and malignant kidney tumors (RCC group vs. BKT group; AUC = 0.989, 0.941, 0.845 and 0.981; Sensitivity = 93.33%, 93.33%, 77.27% and 93.33%; Specificity = 100.00%, 84.21%, 78.38% and 92.11%).

Conclusion: The occurrence of RCC may involve changes in multiple metabolic pathways. The 3-β-D-Galactosyl-sn-glycerol, 7,8-Dihydroneopterin, LPC 19:2 and γ-Aminobutyryl-lysine may be potential biomarkers for the diagnosis or differential diagnosis of RCC.