bluuebunny/crossref_metadata_2025 huggingface dataset:
The circular RNA hsa_circ_000780 as a potential molecular diagnostic target for gastric cancer
Authors: Song Jian , Yu Shuyong , Zhong Dunjing , Yang Weizhong , Jia Zhen , Yuan Guihong , Li Ping , Zhang Ronglin , Li Yini , Zhong Guobing , Chen Zhaowei
Published: November 2021

Background

The present study aimed to identify a specific circular RNA (circRNA) for early diagnosis of gastric cancer (GC).

Methods

Totally 82 patients with GC, 30 with chronic nonatrophic gastritis and 30 with chronic atrophic gastritis were included in this study. Four of the 82 GC patients were selected for screening. Total RNA from malignant and adjacent tissue samples was extracted, and circRNAs in four patients were screened. According to the screening results, the eight most upregulated and downregulated circRNAs with a statistically significant association with GC were identified by real-time fluorescent quantitative polymerase chain reaction (PCR). Then, the most regulated circRNA was selected for further sensitivity and specificity assessments. CircRNA expression was examined by quantitative reverse transcriptase PCR in 78 GC (21 and 57 early and advanced GC, respectively) and adjacent tissue samples, as well as in gastric fluid samples from 30 patients with chronic nonatrophic gastritis, 30 with chronic atrophic gastritis, and 78 GC.

Results

A total of 445 circRNAs, including 69 upregulated and 376 downregulated circRNAs, showed significantly altered expression in GC tissue samples. Hsa_circ_000780 was significantly downregulated in 80.77% of GC tissue samples, with levels in GC tissue samples correlating with tumor size, tumor stage, T stage, venous invasion, carcinoembryonic antigen amounts, and carbohydrate antigen 19–9 levels. Strikingly, this circRNA was found in the gastric fluid of patients with early and advanced GC.

Conclusions

The present study uncovered a new circRNA expression profile in human GC, with hsa_circ_000780 significantly downregulated in GC tissue and gastric fluid specimens. These findings indicate that hsa_circ_000780 should be considered a novel biomarker for early GC screening.
Repurposed pharmacological agents for the potential treatment of COVID-19: a literature review
Authors: Kröker Alina , Tirzīte Madara
Published: November 2021

Background

The COVID-19 pandemic has affected the world extraordinarily. This disease has a potential to cause a significantly severe course of disease leading to respiratory complications, multiple organ failure and possibly death. In the fight against this pandemic-causing disease, medical professionals around the world are searching for pharmacological agents that could treat and prevent disease progression and mortality. To speed the search of promising treatment options, already existing pharmacological agents are repurposed for the potential treatment of COVID-19 and tested in clinical trials. The aim of this literature review is to investigate the efficacy and safety of repurposed pharmacological agents for the treatment of COVID-19 at different pathophysiologic stages of the disease. For this literature review, online-databases PubMed and Google Scholar were utilised. Keywords “COVID-19”, “SARS-CoV-2”, “pathogenesis”, “drug targets”, “pharmacological treatment”, “cytokine storm”, “coagulopathy” and individual drug names were used. Scientific articles, including reviews, clinical trials, and observational cohorts, were collected and analysed. Furthermore, these articles were examined for references to find more clinical trials testing for the potential treatment of COVID-19. In total, 97 references were used to conduct this research paper.

Results

The most beneficial pharmacological agent for the treatment of COVID-19 are corticosteroids, especially dexamethasone, for the treatment of mechanically ventilated COVID-19 patients. Other promising agents are remdesivir for the treatment of patients with COVID-19 pneumonia requiring minimal supplemental oxygen therapy, and IL-6 receptor antagonist monoclonal antibodies in severe COVID-19. Lopinavir/ritonavir, as well as chloroquine or hydroxychloroquine with or without azithromycin demonstrate the least efficacy in the treatment of COVID-19. The clinical benefits of the treatment of a COVID-19-specific coagulopathy with increased dosing of anticoagulation need further research and confirmation of randomised controlled trials.

Conclusion

The search for pharmacological treatment of COVID-19 has elicited great controversy. Whereas drugs like chloroquine, hydroxychloroquine, and lopinavir/ritonavir have not shown proven benefit, the agents remdesivir and dexamethasone are recommended for clinical use for the treatment of COVID-19. Further randomised trials for other pharmacological treatment strategies are awaited.
A short primer on lung stereology
Authors: Ochs Matthias , Schipke Julia
Published: November 2021

The intention of this short primer is to raise your appetite for proper quantitative assessment of lung micro-structure. The method of choice for obtaining such data is stereology. Rooted in stochastic geometry, stereology provides simple and efficient tools to obtain quantitative three-dimensional information based on measurements on nearly two-dimensional microscopic sections. In this primer, the basic concepts of stereology and its application to the lung are introduced step by step along the workflow of a stereological study. The integration of stereology in your laboratory work will help to improve its quality. In a broader context, stereology may also be seen as a contribution to good scientific practice.
A comprehensive approach to stool donor screening for faecal microbiota transplantation in China
Authors: He Jianquan , He Xingxiang , Ma Yonghui , Yang Luxi , Fang Haiming , Shang Shu , Xia Huping , Lian Guanghui , Tang Hailing , Wang Qizhi , Wang Junping , Lin Zhihui , Wen Jianbo , Liu Yuedong , Zhai Chunbao , Wang Wen , Jiang Xueliang , Xuan Ji , Liu Morong , Lu Shiyun , Li Xuejun , Wang Han , Ouyang Cong , Cao Man , Lin Aiqiang , Zhang Bangzhou , Wu Depei , Chen Ye , Xiao Chuanxing
Published: November 2021

Background

Faecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium difficile infections and chronic gastrointestional infections. However, the risks of FMT and the selection process of suitable donors remain insufficiently characterized. The eligibility rate for screening, underlying microbial basis, and core ethical issues of stool donors for FMT are yet to be elucidated in China.

Results

The potential stool donors were screened from December 2017 to December 2019 with the help of an online survey, clinical assessments, and stool and blood testing. Bioinformatics analyses were performed, and the composition and stability of gut microbiota in stool obtained from eligible donors were dynamically observed using metagenomics. Meanwhile, we build a donor microbial evaluation index (DoMEI) for stool donor screening. In the screening process, we also focused on ethical principles and requirements. Of the 2071 participants, 66 donors were selected via the screening process (3.19% success rate). Although there were significant differences in gut microbiota among donors, we found that the changes in the gut microbiota of the same donor were typically more stable than those between donors over time.

Conclusions

DoMEI provides a potential reference index for regular stool donor re-evaluation. In this retrospective study, we summarised the donor recruitment and screening procedure ensuring the safety and tolerability for FMT in China. Based on the latest advances in this field, we carried out rigorous recommendation and method which can assist stool bank and clinicians to screen eligible stool donor for FMT.
Prognostic value and immunological role of AXL gene in clear cell renal cell carcinoma associated with identifying LncRNA/RBP/AXL mRNA networks
Authors: Wang Yi , Tian Ye , Liu Shouyong , Wang Zengjun , Xing Qianwei
Published: November 2021

Backgrounds

This article aimed to explore the prognostic and immunological roles of AXL gene in clear cell renal cell carcinoma (ccRCC) for overall survival (OS) and to identify the LncRNA/RBP/AXL mRNA networks.

Methods

AXL-related gene expression matrix and clinical data were obtained from The Cancer Genome Atlas (TCGA) dataset and AXL-related pathways were identified by gene set enrichment analysis (GSEA). We performed univariate/multivariate Cox regression analysis to evaluate independent prognostic factors and the relationships between AXL and immunity were also investigated.

Results

The outcomes of us indicated that the AXL mRNA expression was up-regulated in ccRCC samples and high expression of AXL was associated with worse OS in TCGA dataset (P < 0.01). Further external verification results from HPA, UALCAN, ICGC dataset, GSE6344, GSE14994, and qRT-PCR remained consistent (all P < 0.05). AXL was also identified as an independent prognostic factor for ccRCC by univariate/multivariate Cox regression analysis (both P < 0.05). A nomogram including AXL expression and clinicopathological factors was established by us and GSEA results found that elevated AXL expression was associated with the JAK-STAT, P53, WNT, VEGF and MAPK signaling pathways. In terms of immunity, AXL was dramatically linked to tumor microenvironment, immune cells, immune infiltration, immune checkpoint molecules and tumor mutational burden (TMB). As for its potential mechanisms, we also identified several LncRNA/RBP/AXL mRNA axes.

Conclusions

AXL was revealed to play prognostic and immunological roles in ccRCC and LncRNA/RBP/AXL mRNA axes were also identified by us for its potential mechanisms.
Clinicopathological and prognostic significance of speckle-type POZ protein in cancers: a systematic review and meta-analysis
Authors: He Yan , Chen Jun , Peng Xingchen , Xia Yanli , Su Yonglin
Published: November 2021

Background

Controversial findings have been reported in the impact of speckle-type POZ protein (SPOP) on clinicopathological features and prognosis in diverse cancers. We conducted this meta-analysis to confirm whether SPOP was an effective biomarker to predict clinical stage, cancer differentiation and survival.

Methods

We searched studies published before June 2021 through Medline, Embase, the Cochrane library register of controlled trials and Wanfang databases. The corrections of SPOP expression with expression disparity, tumor differentiation, clinical stage and survival were analyzed.

Results

Our meta-analysis found that higher expression of SPOP was significantly associated with earlier clinical stage, well differentiation and better overall survival. Subgroup analysis showed that the SPOP expression of adjacent tissue was significantly higher than that in cancer tissues of prostate and liver. However, renal cancer presented improved expression of SPOP in cancer tissue.

Conclusions

SPOP has the potential function to act as a novel and effective biomarker for cancer diagnosis and prognostic stratification.
PESV represses non-small cell lung cancer cell malignancy through circ_0016760 under hypoxia
Authors: Zhang Hong , Zhang Haojian , Zhu Jiye , Liu Huan , Zhou Qin
Published: November 2021

Background

Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancers, which is the most common malignant tumor worldwide. Polypeptide extract from scorpion venom (PESV) has been reported to inhibit NSCLC process. The present study aims to reveal the roles of PESV in NSCLC progression under hypoxia and the inner mechanism.

Methods

The expression levels of circular RNA 0016760 (circ_0016760) and microRNA-29b (miR-29b) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was determined by western blot and immunohistochemistry assays. Cell migration, invasion, proliferation and tube formation were investigated by transwell, cell colony formation, 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide and tube formation assays. The impacts between PESV and circ_0016760 overexpression on tumor growth in vivo were investigated by in vivo tumor formation assay.

Results

Circ_0016760 expression was dramatically upregulated in NSCLC tissues and cells, compared with adjacent lung tissues and cells, respectively. PESV treatment downregulated circ_0016760 expression. Circ_0016760 silencing or PESV treatment repressed cell migration, invasion, proliferation and tube formation under hypoxia in NSCLC cells. Circ_0016760 overexpression restored the effects of PESV treatment on NSCLC process under hypoxia. Additionally, circ_0016760 acted as a sponge of miR-29b, and miR-29b bound to HIF1A. Meanwhile, miR-29b inhibitor impaired the influences of circ_0016760 knockdown on NSCLC process under hypoxia. Further, ectopic circ_0016760 expression restrained the effects of PESV exposure on tumor formation in vivo.

Conclusion

Circ_0016760 overexpression counteracted PESV-induced repression of NSCLC cell malignancy and angiogenesis under hypoxia through miR-29b/HIF1A axis.
Let-7a induces metabolic reprogramming in breast cancer cells via targeting mitochondrial encoded ND4
Authors: Sharma Praveen , Sharma Vibhuti , Ahluwalia Tarunveer Singh , Dogra Nilambra , Kumar Santosh , Singh Sandeep
Published: November 2021

Background and objectives

MicroRNA (miRNA) that translocate from the nucleus to mitochondria are referred to as mitochondrial microRNA (mitomiR). Albeit mitomiRs have been shown to modulate gene expression, their functional impact within mitochondria is unknown. The main objective of this study is to investigate whether the mitochondrial genome is regulated by miR present inside the mitochondria.

Methods and results

Here, we report mitomiR let-7a regulates mitochondrial transcription in breast cancer cells and reprogram the metabolism accordingly. These effects were mediated through the interaction of let-7a with mtDNA, as studied by RNA pull-down assays, altering the activity of Complex I in a cell line-specific manner. Our study, for the first time, identifies the role of mitomiR (let-7a) in regulating the mitochondrial genome by transcriptional repression and its contribution to regulating mitochondrial metabolism of breast cancer cells.

Conclusion

These findings uncover a novel mechanism by which mitomiR regulates mitochondrial transcription.
TMED3/RPS15A Axis promotes the development and progression of osteosarcoma
Authors: Xu Wei , Li Yifan , Ye Xiaojian , Ji Yunhan , Chen Yu , Zhang Xiangyang , Li Zhikun
Published: November 2021

Background

Osteosarcoma is a primary malignant tumor that mainly affects children and young adults. Transmembrane emp24 trafficking protein 3 (TMED3) may be involved in the regulation of malignant cancer behaviors. However, the role of TMED3 in osteosarcoma remains mysterious. In this study, the potential biological function and underlying mechanism of TMED3 in progression of osteosarcoma was elaborated.

Methods

The expression of TMED3 in osteosarcoma was analyzed by immunohistochemical staining. The biological function of TMED3 in osteosarcoma was determined through loss-of-function assays in vitro. The effect of TMED3 downregulation on osteosarcoma was further explored by xenograft tumor model. The molecular mechanism of the regulation of TMED3 on osteosarcoma was determined by gene expression profile analysis.

Results

The expression of TMED3 in osteosarcoma tissues was significantly greater than that in matched adjacent normal tissues. Knockdown of TMED3 inhibited the progression of osteosarcoma by suppressing proliferation, impeding migration and enhancing apoptosis in vitro. We further validated that knockdown of TMED3 inhibited osteosarcoma generation in vivo. Additionally, ribosomal protein S15A (RPS15A) was determined as a potential downstream target for TMED3 involved in the progression of osteosarcoma. Further investigations elucidated that the simultaneous knockdown of RPS15A and TMED3 intensified the inhibitory effects on osteosarcoma cells. Importantly, knockdown of RPS15A alleviated the promotion effects of TMED3 overexpression in osteosarcoma cells.

Conclusions

In summary, these findings emphasized the importance of TMED3/RPS15A axis in promoting tumor progression, which may be a promising candidate for molecular therapy of osteosarcoma.
NEDD4L-induced ubiquitination mediating UBE2T degradation inhibits progression of lung adenocarcinoma via PI3K-AKT signaling
Authors: Chen Yongbing , Hong Haihua , Wang Qingqing , Li Junqiang , Zhang Wenfeng , Chen Tingting , Li Pu
Published: November 2021

Background

A number of studies have indicated that Ubiquitin-conjugating enzyme E2T (UBE2T), as an oncogene, promotes progression and metastasis of lung cancer, including lung adenocarcinoma (LUAD), but it is completely unknown whether and how UBE2T is ubiquitylated and degraded, and by which E3 ligase. NEDD4L plays a critical role in the regulation of cellular processes of various cancers, most of which is attributed to its E3 ubiquitin ligase function. However, the relationship between NEDD4L and UBE2T in LUAD has not been elucidated.

Methods

The relationship between NEDD4L and UBE2T in LUAD tissues and cells was found by bioinformatic analyses and immunoblotting. Cell counting kit-8, colony formation assay, half-life analysis and the in vivo ubiquitylation assay, generation of xenograft model were performed to determine how NEDD4L regulates UBE2T and its downstream signaling pathway in vitro and in vivo.

Results

Bioinformatic analyses found that NEDD4L, as a potential correlation E3 ligase of UBE2T, was negatively correlated with UBE2T in LUAD. Consistently, UBE2T protein half-life was shortened or extended by NEDD4L overexpression or depletion, respectively. NEDD4L inhibited LUAD cell progression in vitro and in vivo via inducing the ubiquitination-mediated UBE2T degradation, which repressed PI3K-AKT signaling. Similarly, NEDD4L predicted a better patient survival, whereas UBE2T predicted a worse survival.

Conclusions

Collectively, our results reveal that NEDD4L is a novel E3 ligase of UBE2T, which can inhibit PI3K-AKT signaling by targeting for UBE2T ubiquitination and degradation, resulting in repression of LUAD cell progression.
To explore immune synergistic function of Quercetin in inhibiting breast cancer cells
Authors: Qiu Dan , Yan Xianxin , Xiao Xinqin , Zhang Guijuan , Wang Yanqiu , Cao Jingyu , Ma Ruirui , Hong Shouyi , Ma Min
Published: November 2021

Background

The precancerous disease of breast cancer is an inevitable stage in the tumorigenesis and development of breast neoplasms. Quercetin (Que) has shown great potential in breast cancer treatment by inhibiting cell proliferation and regulating T cell function. γδ T cells are a class of nontraditional T cells that have long attracted attention due to their potential in immunotherapy. In this study, we revealed the immunomodulatory function of Que through regulation of the JAK/STAT1 signaling pathway, which was followed by the synergistic killing of breast cancer cells.

Methods

In the experimental design, we first screened target genes with or without Que treatment, and we intersected the Que target with the disease target by functional enrichment analysis. Second, MCF-10A, MCF-10AT, MCF-7 and MDA-MB-231 breast cancer cell lines were treated with Que for 0 h, 24 h and 48 h. Then, we observed the expression of its subsets by coculturing Que and γδ T cells and coculturing Que and γδ T cells with breast tumor cells to investigate their synergistic killing effect on tumor cells. Finally, Western blotting was used to reveal the changes in proteins related to the JAK/STAT1 signaling pathway after Que treatment in MCF-10AT and MCF-7 cells for 48 h.

Results

The pathway affected by Que treatment was the JAK/STAT1 signaling pathway and was associated with precancerous breast cancer, as shown by network pharmacology analysis. Que induced apoptosis of MCF-10AT, MCF-7 and MDA-MB-231 cells in a time- and concentration-dependent manner (P < 0.05). Most importantly, Que promoted the differentiation of γδ T cells into the Vδ2 T cell subpopulation. The best ratio of effector cells to target cells (E/T) was 10:1, the killing percentages of γδ T cells against MCF-10A, MCF-10AT, MCF-7, and MDA-MB-231 were 61.44 ± 4.70, 55.52 ± 3.10, 53.94 ± 2.74, and 53.28 ± 1.73 (P = 0.114, P = 0.486,andP = 0.343, respectively), and the strongest killing effect on precancerous breast cancer cells and breast cancer cells was found when the Que concentration was 5 μM and the E/T ratio was 10:1 (64.94 ± 3.61, 64.96 ± 5.45, 55.59 ± 5.98, and 59.04 ± 5.67, respectively). In addition, our results showed that Que increased the protein levels of IFNγ-R, p-JAK2 and p-STAT1 while decreasing the protein levels of PD-L1 (P < 0.0001).

Conclusions

In conclusion, Que plays a synergistic role in killing breast cancer cells and promoting apoptosis by regulating the expression of IFNγ-R, p-JAK2, p-STAT1 and PD-L1 in the JAK/STAT1 signaling pathway and promoting the regulation of γδ T cells. Que may be a potential drug for the prevention of precancerous breast cancer and adjuvant treatment of breast cancer.
Bioinformatics prediction and experimental verification identify MAD2L1 and CCNB2 as diagnostic biomarkers of rhabdomyosarcoma
Authors: Xia Tian , Meng Lian , Zhao Zhijuan , Li Yujun , Wen Hao , Sun Hao , Zhang Tiantian , Wei Jingxian , Li Feng , Liu Chunxia
Published: November 2021

Background

Rhabdomyosarcoma (RMS) is a malignant soft-tissue tumour. In recent years, the tumour microenvironment (TME) has been reported to be associated with the development of tumours. However, the relationship between the occurrence and development of RMS and TME is unclear. The purpose of this study is to identify potential tumor microenvironment-related biomarkers in rhabdomyosarcoma and analyze their molecular mechanisms, diagnostic and prognostic significance.

Methods

We first applied bioinformatics method to analyse the tumour samples of 125 patients with rhabdomyosarcoma (RMS) from the Gene Expression Omnibus database (GEO). Differential genes (DEGs) that significantly correlate with TME and the clinical staging of tumors were extracted. Immunohistochemistry (IHC) was applied to validate the expression of mitotic arrest deficient 2 like 1 (MAD2L1) and cyclin B2 (CCNB2) in RMS tissue. Then, we used cell function and molecular biology techniques to study the influence of MAD2L1 and CCNB2 expression levels on the progression of RMS.

Results

Bioinformatics results show that the RMS TME key genes were screened, and a TME-related tumour clinical staging model was constructed. The top 10 hub genes were screened through the establishment of a protein–protein interaction (PPI) network, and then Gene Expression Profiling Interactive Analysis (GEPIA) was conducted to measure the overall survival (OS) of the 10 hub genes in the sarcoma cases in The Cancer Genome Atlas (TCGA). Six DEGs of statistical significance were acquired. The relationship between these six differential genes and the clinical stage of RMS was analysed. Further analysis revealed that the OS of RMS patients with high expression of MAD2L1 and CCNB2 was worse and the expression of MAD2L1 and CCNB2 was related to the clinical stage of RMS patients. Gene set enrichment analysis (GSEA) revealed that the genes in MAD2L1 and CCNB2 groups with high expression were mainly related to the mechanism of tumour metastasis and recurrence. In the low-expression MAD2L1 and CCNB2 groups, the genes were enriched in the metabolic and immune pathways. Immunohistochemical results also confirmed that the expression levels of MAD2L1 (30/33, 87.5%) and CCNB2 (33/33, 100%) were remarkably higher in RMS group than in normal control group (0/11, 0%). Moreover, the expression of CCNB2 was related to tumour size. Downregulation of MAD2L1 and CCNB2 suppressed the growth, invasion, migration, and cell cycling of RMS cells and promoted their apoptosis. The CIBERSORT immune cell fraction analysis indicated that the expression levels of MAD2L1 and CCNB2 affected the immune status in the TME.

Conclusions

The expression levels of MAD2L1 and CCNB2 are potential indicators of TME status changes in RMS, which may help guide the prognosis of patients with RMS and the clinical staging of tumours.
High prevalence of malaria in a non-endemic setting among febrile episodes in travellers and migrants coming from endemic areas: a retrospective analysis of a 2013–2018 cohort
Authors: Garcia-Ruiz de Morales Alejandro , Morcate Covadonga , Isaba-Ares Elena , Perez-Tanoira Ramon , Perez-Molina Jose A.
Published: November 2021

Background

The study aimed to analyse the likelihood of imported malaria in people with a suggestive clinical picture and its distinctive characteristics in a hospital in the south of Madrid, Spain.

Methods

Observational retrospective study that consisted of a review of all medical files of patients with any malaria test registered at Móstoles University Hospital between April 2013 and April 2018. All suspected malaria cases were confirmed by Plasmodium spp. polymerase chain reaction (PCR).

Results

Of the 328 patients with suspected malaria (53.7% migrant-travellers; 38.7% visitors; 7.6% travellers), 108 cases were confirmed (101 by Plasmodium falciparum), accounting for a 33% positive sample rate. Sixteen cases were diagnosed only by PCR. Patients with malaria, compared to those without, presented predominantly with fever (84% vs. 65%), were older (34 vs. 24 years), sought medical attention earlier (17d vs. 32d), had a greater number of previous malaria episodes (74% vs. 60%), lower levels of platelets (110,500µL vs. 250,000µL), and higher of bilirubin (0.6 mg/dL vs. 0.5 mg/dL). Severe malaria was present in 13 cases; no deaths were recorded. Malaria diagnosis showed a bimodal distribution with two peaks: June to September and November to January.

Conclusions

Malaria is still a common diagnosis among febrile patients coming from the tropics specially among migrant travellers. Fever, thrombocytopenia, and/or high bilirubin levels should raise suspicion for this parasitic infection. Prompt diagnosis is crucial to avoid severe cases and deaths.
Assessing health-seeking behaviour and malaria prevention practices among communities in four districts of the Volta Region of Ghana
Authors: Orish Verner N. , Maalman Raymond Saa-Eru , Donkor Otchere Y. , Ceruantes Barbara Yordanis Henandez , Osei Eric , Amu Hubert , Appiah Prince Kubi , Konlan Kennedy Diema , Mumuni Hadiru , Kim Eunji , Kim Siwoo , Jung Hajun , Ofori-Amoah Jones , Kofie Philip , Adjuik Martin , Alhassan Robert Kaba , Donkor Ernestina Safoa , Zottor Francis Bruno , Kweku Margaret , Amuna Paul , Kim So Yoo , Gyapong John Owusu ,   the UHAS-Yonsei Project Team
Published: November 2021

Background

Malaria is a preventable disease that causes huge morbidity and mortality in malaria-endemic areas, especially among children and pregnant women. The malaria control programme focuses on the prevention of mosquito bites using insecticide-treated nets (ITNs) and mosquito aerosol sprays and coils, as well as prevention of severe disease among those infected through prompt and adequate treatment. The success of the malaria control programme in Ghana is dependent on the malaria prevention practices of people in the community. Therefore, this study evaluated the malaria prevention practices of participants in four districts of the Volta Region of Ghana.

Methods

This was a cross-sectional study conducted in Ketu South, Nkwanta South, Hohoe Municipality and Ho West districts of the Volta Region of Ghana. Questionnaire were administered to adults who consented to each household visited. Questions were asked on the socio-demographics and malaria prevention practices of the households. Data analysis was done using SPSS version 23 with frequency distribution done for all the variables. Pearson chi-square was used to determine the significant association between socio-demographics and malaria prevention practices, and Multivariate nominal logistic regression analysis was used to model the relationship between dichotomous dependent variables (ITN ownership and usage) and independent variables.

Results

Out of the 2493 participants; 2234 (89.6%) owned ITN and 1528 (68.4%) used ITN a night before this study, 768 (30.8%) used mosquito aerosol spray and 368 (15%) used mosquito coil. More females significantly owned ITN than males (1293, 92.4%, p ≤ 0.001). Participants from Ketu South had 1.5 times higher odds of owning an ITN compared to Ho West whose odds are not different from Nkwanta South or Hohoe (AOR, 1.56 [95% 1.09–2.22]; p = 0.01). In terms of ITN usage, participants in Nkwanta South were less likely to use ITN compared to the other districts; AOR, 0.434 [95% CI 0.31–0.62, p < 0.001]. Also, of the 668 participants that had a fever within the past 3 days, 268 (40.1%) visited a patent medicine store and 156 (23.4%) visited health facilities.

Conclusion

There is high ownership of ITNs, but relatively low utilization among the community members. Education on malaria prevention practices should be intensified and continuous among the population of the Volta Region to ensure the success of malaria control in the region.
Long-term training on sand changes lower limb muscle activities during running in runners with over-pronated feet
Authors: Jafarnezhadgero AmirAli , Fatollahi Amir , Sheykholeslami Ali , Dionisio Valdeci Carlos , Akrami Mohammad
Published: November 2021

Background

Running on sand could be a promising exercise intervention for the treatment of over-pronated feet. However, there is a lack of knowledge about the effects of running on sand on muscle activities. Therefore, this study aims to evaluate the long-term effects of running on sand on the activities of selected lower limb muscles in individuals with OPF compared with healthy controls.

Methods

Sixty recreational adult male runners with over-pronated feet (foot posture index > 10) were divided into two equal groups (intervention and control). Participants ran barefoot at a pre-defined speed (⁓3.3 m/s) over level stable ground both before and after long-term training on the sand. Muscle activities were recorded using a surface bipolar electromyography system.

Results

For the intervention group, we found a reduced foot posture index (p < 0.001; d = 2.00) and significant group-by-time interactions for gluteus medius activity during the mid-stance phase (p < 0.028; d = 0.59). Significantly higher gluteus medius activity (p = 0.028, d = 0.569) was found during the post-test. We also observed significant group-by-time interactions for medial gastrocnemius activity during the push-off phase (p < 0.041; d = 0.54). Significantly larger medial gastrocnemius activity (p = 0.041; d = 0.636) was found during the post-test compared to the pre-test.

Conclusions

Long-term running on sand resulted in reduced pronation, increased medial gastrocnemius activity, and improved frontal plane pelvic stability due to higher gluteus medius activity.

Trial registration: IRCT20191211045704N1. Registered 25 February 2020. Retrospectively registered.
Effect of limb rotation on radiographic alignment measurement in mal-aligned knees
Authors: Sun Xiaoshu , Yang Bin , Xiao Shengzhao , Yan Yichen , Liu Zifan , Yuan Liang , Wang Xiaohua , Sun Bin , Yao Jie , Fan Yubo
Published: November 2021

Purpose

Long-leg-radiography (LLR) is commonly used for the measurement of lower limb alignment. However, limb rotations during radiography may interfere with the alignment measurement. This study examines the effect of limb rotation on the accuracy of measurements based on the mechanical and anatomical axes of the femur and tibia, with variations in knee flexion and coronal deformity.

Methods

Forty-five lower limbs of 30 patients were scanned with CT. Virtual LLRs simulating five rotational positions (neutral, ± 10$$^{\circ }$$

∘

, and ± 20$$^{\circ }$$

∘

internal rotation) were generated from the CT images. Changes in the hip–knee–ankle angle (HKA) and the femorotibial angle (FTA) were measured on each image with respect to neutral values. These changes were related to knee flexion and coronal deformity under both weight- and non-weight-bearing conditions.

Results

The measurement errors of the HKA and FTA derived from limb rotation were up to 4.84 ± 0.66$$^{\circ }$$

∘

and 7.35 ± 0.88$$^{\circ }$$

∘

, respectively, and were correlated with knee flexion (p < 0.001) and severe coronal deformity (p < 0.001). Compared with the non-weight-bearing position, the coronal deformity measured in the weight-bearing condition was 2.62$$^{\circ }$$

∘

greater, the correlation coefficients between the coronal deformity and the deviation ranges of HKA and FTA were also greater.

Conclusions

Flexion and severe coronal deformity have a significant influence on the measurement error of lower limb alignment. Errors can be amplified in the weight-bearing condition compared with the non-weight-bearing condition. When using HKA and FTA to represent the mechanical axis and the anatomical axis on LLR, limb rotation impacts the anatomic axis more than the mechanical axis in patients with severe deformities. Considering LLR as the gold standard image modality, attention should be paid to the measurement of knee alignment. Especially for the possible errors derived from weight-bearing long-leg radiographs of patients with severe knee deformities.
Dysregulation of alternative splicing is associated with the pathogenesis of ulcerative colitis
Authors: Li Daowei , Tan Yue
Published: November 2021

Background

Although numerous risk loci for ulcerative colitis (UC) have been identified in the human genome, the pathogenesis of UC remains unclear. Recently, multiple transcriptomic analyses have shown that aberrant gene expression in the colon tissues of UC patients is associated with disease progression. A pioneering study also demonstrated that altered post-transcriptional regulation is involved in the progression of UC. Here, we provide a genome-wide analysis of alternative splicing (AS) signatures in UC patients. We analyzed three datasets containing 74 tissue samples from UC patients and identified over 2000 significant AS events.

Results

Skipped exon and alternative first exon were the two most significantly altered AS events in UC patients. The immune response-related pathways were remarkably enriched in the UC-related AS events. Genes with significant AS events were more likely to be dysregulated at the expression level.

Conclusions

We present a genomic landscape of AS events in UC patients based on a combined analysis of two cohorts. Our results indicate that dysregulation of AS may have a pivotal role in determining the pathogenesis of UC. In addition, our study uncovers genes with potential therapeutic implications for UC treatment.
Prenatal ambient air pollution and maternal depression at 12 months postpartum in the MADRES pregnancy cohort
Authors: Bastain Theresa M. , Chavez Thomas , Habre Rima , Hernandez-Castro Ixel , Grubbs Brendan , Toledo-Corral Claudia M. , Farzan Shohreh F. , Lurvey Nathana , Lerner Deborah , Eckel Sandrah P. , Lurmann Fred , Lagomasino Isabel , Breton Carrie
Published: November 2021

Background

Depression is the leading cause of mental health-related morbidity and affects twice as many women as men. Hispanic/Latina women in the US have unique risk factors for depression and they have lower utilization of mental health care services. Identifying modifiable risk factors for maternal depression, such as ambient air pollution, is an urgent public health priority. We aimed to determine whether prenatal exposure to ambient air pollutants was associated with maternal depression at 12 months after childbirth.

Methods

One hundred eighty predominantly low-income Hispanic/Latina women participating in the ongoing MADRES cohort study in Los Angeles, CA were followed from early pregnancy through 12 months postpartum through a series of phone questionnaires and in-person study visits. Daily prenatal ambient pollutant estimates of nitrogen dioxide (NO2), ozone (O3), and particulate matter (PM10 and PM2.5) were assigned to participant residences using inverse-distance squared spatial interpolation from ambient monitoring data. Exposures were averaged for each trimester and across pregnancy. The primary outcome measure was maternal depression at 12 months postpartum, as reported on the 20-item Center for Epidemiologic Studies-Depression (CES-D) scale. We classified each participant as depressed (n = 29) or not depressed (n = 151) based on the suggested cutoff of 16 or above (possible scores range from 0 to 60) and fitted logistic regression models, adjusting for potential confounders.

Results

We found over a two-fold increased odds of depression at 12 months postpartum associated with second trimester NO2 exposure (OR = 2.63, 95% CI: 1.41–4.89) and pregnancy average NO2 (OR = 2.04, 95% CI: 1.13–3.69). Higher second trimester PM2.5 exposure also was associated with increased depression at 12 months postpartum (OR = 1.56, 95% CI: 1.01–2.42). The effect for second trimester PM10 was similar and was borderline significant (OR = 1.58, 95% CI: 0.97–2.56).

Conclusions

In a low-income cohort consisting of primarily Hispanic/Latina women in urban Los Angeles, we found that prenatal ambient air pollution, especially mid-pregnancy NO2 and PM2.5, increased the risk of depression at 12 months after childbirth. These results underscore the need to better understand the contribution of modifiable environmental risk factors during potentially critical exposure periods.
A new phenotypic classification system for dyslipidemias based on the standard lipid panel
Authors: Sampson Maureen , Ballout Rami A. , Soffer Daniel , Wolska Anna , Wilson Sierra , Meeusen Jeff , Donato Leslie J. , Fatica Erica , Otvos James D. , Brinton Eliot A. , Rosenson Robert S. , Wilson Peter , Amar Marcelo , Shamburek Robert , Karathanasis Sotirios K. , Remaley Alan T.
Published: November 2021

Background

Dyslipoproteinemias can be classified by their distinct lipoprotein patterns, which helps determine atherosclerotic cardiovascular disease (ASCVD) risk and directs lipid management but this has required advanced laboratory testing.

Objective

To develop a new algorithm for classifying lipoprotein disorders that only relies on the standard lipid panel.

Methods

Lipid thresholds for defining the different lipoprotein phenotypes were derived for Non-High-Density Lipoprotein-Cholesterol (NonHDL-C) and Triglycerides (TG) to be concordant when possible with the current US Multi-Society guidelines for blood cholesterol management.

Results

The new classification method categorizes patients into all the classical Fredrickson-like phenotypes except for Type III dysbetalipoproteinemia. In addition, a new hypolipidemic phenotype (Type VI) due to genetic mutations in apoB-metabolism is described. The validity of the new algorithm was confirmed by lipid analysis by NMR (N = 11,365) and by concordance with classification by agarose gel electrophoresis/beta-quantification (N = 5504). Furthermore, based on the Atherosclerosis Risk in Communities (ARIC) cohort (N = 14,742), the lipoprotein phenotypes differ in their association with ASCVD (TypeV>IIb > IVb > IIa > IVa > normolipidemic) and can be used prognostically as risk enhancer conditions in the management of patients.

Conclusions

We describe a clinically useful lipoprotein phenotyping system that is only dependent upon the standard lipid panel. It, therefore, can be easily implemented for increasing compliance with current guidelines and for improving the care of patients at risk for ASCVD.
Associations of visit-to-visit variabilities and trajectories of serum lipids with the future probability of type 2 diabetes mellitus
Authors: Sun Qian , Liu Jingchao , Wu Lei , Sun Yue , Jin Jianrong , Wang Sudan , Wu Jing , Jing Yang , Zhou Hui , Dong Chen
Published: November 2021

Background

Serum lipid abnormalities are generally considered as a major risk factor for type 2 diabetes mellitus (T2DM). However, evidence for the effect of long-term serum lipid fluctuations on future T2DM probability remains limited.

Methods

A total of 4475 nondiabetic participants who underwent annual health examinations between 2010 and 2013 were followed for the subsequent 5-year risk of T2DM. The Cox proportional hazards model was performed to evaluate the associations of visit-to-visit variabilities and trajectories of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) with T2DM probability.

Results

During the five-year follow-up, 223 newly developed T2DM cases were identified. Compared with the “Low” TG trajectory, “Moderate” and “Moderate-High” TG trajectories were significantly associated with T2DM incidence, with adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) of 1.51 (1.12-2.03) and 2.55 (1.62-4.03), respectively. Additionally, participants in the third and fourth quartiles of TG/standard deviation (SD) were associated with increased T2DM probability when compared with those in the lowest quartile. After excluding individuals with prediabetes, participants with “Moderate-High” TG trajectory still had a 2.43-fold greater risk of T2DM compared with those with “Low” TG trajectory (95 % CI: 1.28-4.63). In addition, compared with participants in “Low” HDL-c trajectory, the future T2DM probability was significantly reduced in those with “Moderate” and “High” HDL-c trajectories, with HR (95 % CI) of 0.52 (0.37-0.72) and 0.38 (0.18-0.80), respectively. After excluding individuals with prediabetes, the “Moderate” HDL-c trajectory remained associated with decreased T2DM probability when compared with “Low” HDL-c trajectory (HR: 0.55, 95 % CI: 0.35-0.88). However, the incidence of T2DM was not associated with the long-term fluctuations of TC and LDL-c.

Conclusions

Long-term visit-to-visit variability of TG, and the change trajectories of TG and HDL-c were significantly associated with future T2DM probability. Moreover, these associations were not affected after excluding individuals with prediabetes.
Application of nanotechnology in the diagnosis and treatment of bladder cancer
Authors: Xu Yadong , Luo Cheng , Wang Jieqiong , Chen Lingwu , Chen Junxing , Chen Tianfeng , Zeng Qinsong
Published: November 2021

Bladder cancer (BC) is a common malignancy in the genitourinary system and the current theranostic approaches are unsatisfactory. Sensitivity and specificity of current diagnosis methods are not ideal and high recurrence and progression rates after initial treatment indicate the urgent need for management improvements in clinic. Nanotechnology has been proposed as an effective method to improve theranosis efficiency for both non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). For example, gold nanoparticles (AuNPs) have been developed for simple, fast and sensitive urinary sample test for bladder cancer diagnosis. Nanoparticles targeting bladder cancers can facilitate to distinguish the normal and abnormal bladder tissues during cystoscopy and thus help with the complete removal of malignant lesions. Both intravenous and intravesical agents can be modified by nanotechnology for targeted delivery, high anti-tumor efficiency and excellent tolerability, exhibiting encouraging potential in bladder cancer treatment. Photosensitizers and biological agents can also be delivered by nanotechnology, intermediating phototherapy and targeted therapy. The management of bladder cancer remained almost unchanged for decades with unsatisfactory effect. However, it is likely to change with the fast-developed nanotechnology. Herein we summarized the current utility of nanotechnology in bladder cancer diagnosis and treatment, providing insights for the future designing and discovering novel nanoparticles for bladder cancer management.

Graphical Abstract
Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine
Authors: Han Shulan , Ma Wenyan , Jiang Dawei , Sutherlin Logan , Zhang Jing , Lu Yu , Huo Nan , Chen Zhao , Engle Jonathan W. , Wang Yanping , Xu Xiaojie , Kang Lei , Cai Weibo , Wang Lianyan
Published: November 2021

Background

Poly(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles have potential applications as a vaccine adjuvant and delivery system due to its unique advantages as biodegradability and biocompatibility.

Experimental

We fabricated cationic solid lipid nanoparticles using PLGA and dimethyl-dioctadecyl-ammonium bromide (DDAB), followed by loading of model antigen OVA (antigen ovalbumin, OVA257-264) to form an OVA@DDAB/PLGA nano-vaccine. And we investigated the intracellular signaling pathway in dendritic cells in vitro and antigen transport pathway and immune response in vivo mediated by an OVA@DDAB/PLGA nano-vaccine.

Results

In vitro experiments revealed that the antigen uptake of BMDCs after nanovaccine incubation was two times higher than pure OVA or OVA@Al at 12 h. The BMDCs were well activated by p38 MAPK signaling pathway. Furthermore, the nano-vaccine induced antigen escape from lysosome into cytoplasm with 10 times increased cross-presentation activity than those of OVA or OVA@Al. Regarding the transport of antigen into draining lymph nodes (LNs), the nano-vaccine could rapidly transfer antigen to LNs by passive lymphatic drainage and active DC transport. The antigen+ cells in inguinal/popliteal LNs for the nano-vaccine were increased over two folds comparing to OVA@Al and OVA at 12 h. Moreover, the antigen of nano-vaccine stayed in LNs for over 7 days, germinal center formation over two folds higher than those of OVA@Al and OVA. After immunization, the nano-vaccine induced a much higher ratio of IgG2c/IgG1 than OVA@Al. It also effectively activated CD4+ T, CD8+ T and B cells for immune memory with a strong cellular response.

Conclusion

These results indicated that DDAB/PLGA NP was a potent platform to improve vaccine immunogenicity by p38 signaling pathway in BMDCs, enhancing transport of antigens to LNs, and higher immunity response.

Graphical Abstract
Reactive oxygen species (ROS)-responsive nanoprobe for bioimaging and targeting therapy of osteoarthritis
Authors: Shen Chong , Gao Ming , Chen Haimin , Zhan Yanting , Lan Qiumei , Li Zhimin , Xiong Wei , Qin Zainen , Zheng Li , Zhao Jinmin
Published: November 2021

Stimulus-responsive therapy that allows precise imaging-guided therapy is limited for osteoarthritis (OA) therapy due to the selection of proper physiological markers as stimulus. Based on that the over-production of Reactive Oxygen Species (ROS) is associated with the progression in OA, we selected ROS as markers and designed a cartilage targeting and ROS-responsive theranostic nanoprobe that can be used for effective bioimaging and therapy of OA. This nanoprobe was fabricated by using PEG micelles modified with ROS-sensitive thioketal linkers (TK) and cartilage-targeting peptide, termed TKCP, which was then encapsulated with Dexamethasone (DEX) to form TKCP@DEX nanoparticles. Results showed that the nanoprobe can smartly “turn on” in response to excessive ROS and “turn off” in the normal joint. By applying different doses of ROS inducer and ROS inhibitor, this nanoprobe can emit ROS-dependent fluorescence according to the degree of OA severity, helpful to precise disease classification in clinic. Specifically targeting cartilage, TKCP@DEX could effectively respond to ROS and sustained release DEX to remarkably reduce cartilage damage in the OA joints. This smart, sensitive and endogenously activated ROS-responsive nanoprobe is promising for OA theranostics.

Graphical Abstract