bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cultural significance of medicinal plants in healing human ailments among Guji semi-pastoralist people, Suro Barguda District, Ethiopia
Authors: Eshete Mersha Ashagre , Molla Ermias Lulekal 
Published: October 2021

Abstract
Background
Traditional medicine has remained the most affordable and easily accessible source of treatment in the primary healthcare system among communities unable to get modern medication. Ethiopian indigenous people have a long history of traditional plant utilization for treating ailments. The objectives of this study were to identify, document, and analyze the cultural significances of medicinal plants and their associated indigenous knowledge among Guji Semi-Pastoralist People, in Suro Barguda District, West Guji Zone, southern Ethiopia.

Methods
Semi-structured interview, focus group discussions, participant observation, and walk-in-the-woods methods were used to gather medicinal plants data. The informant consensus factor (ICF) and fidelity level (FL) values were calculated using quantitative approaches to check the level of informants' agreement on plant use and the healing potential of medicinal plant species, respectively. Indigenous knowledge of the use of medicinal plants for medicinal purposes among different informant groups was compared using t tests with R software.

Results
A total of 98 medicinal plant species belonging to 87 genera and 48 families were reported to be used for treating human ailments such as gastrointestinal diseases, breathing system diseases, dermatological diseases, and febrile diseases. Family Fabaceae was represented by 10 species followed by Lamiaceae (7 species). Four of the medicinal plants (Bothriocline schimperi Oliver & Hiern ex Bentham, Erythrina brucei Schweinf. emend. Gillett, Lippia adoensis Hochst. ex Walp. var. adoensis, and Millettia ferruginea (Hochst.) Hochst. ex Baker) were found endemic to Ethiopia and shrubs were more dominant (36 species). Ninety-one medicinal plant species were used for remedy preparation as soon as they were collected in their fresh form; 35.6% herbal medicine preparation was through crushing the plant parts and homogenizing them with cold and clean water; 159 (70.4%) traditional medicinal preparations were reported to be taken in their drinking form (orally).

Conclusion
The study indicated that the district is rich in different species of medicinal plants used to treat human ailments and indigenous knowledge about using these resources. Species with the recorded highest consensus for curative purposes are useful sources for further phytochemical and pharmacological validation for better utilization. Declining wild medicinal flora of the area calls for conservation priority.
Does breastfeeding protect children from COVID-19? An observational study from pediatric services in Majorca, Spain
Authors: Verd Sergio , Ramakers Jan , Vinuela Isabel , Martin-Delgado Maria-Isabel , Prohens Aina , Díez Ruth 
Published: October 2021

Abstract
Background
It has been demonstrated that children who had been breastfed remain better protected against various infections, and notably respiratory tract infections, well beyond infancy. Since the role of breastfeeding to explain why children are less affected by COVID-19 has not been studied until now, the aim of this study was to determine whether any history of breastfeeding reduces the incidence rate of COVID-19 in children.

Methods
This was a secondary analysis of an observational study on clinical and epidemiological characteristics of pediatric COVID-19 in Majorca. A total of 691 children were recruited during the 5 months of August–December 2020. Eligible participants were children under 14 who were tested for SARS-CoV-2 in pediatric emergency services. The independent explanatory variable was any breastfeeding. Bivariate analyses were conducted through the Chi-square test, the Fisher’s Exact test or the Student’s T test.
All children had the same demographic, epidemiological and clinical data collected through a study team member interview and via the participants medical records.

Results
Within the sample of children who visited emergency services with symptoms of potential COVID-19, we found higher prevalence of positive SARS-CoV-2 RT-PCR test results among those who were exclusively formula fed compared with those who were ever breastfed (OR 2.48; 95% CI 1.45, 3.51; P = 0.036).

Conclusions
The present study suggests that ever breastfeeding reduces the risk of COVID-19 among children, as documented for other infections.
Association of total testosterone status with bone mineral density in adults aged 40–60 years
Authors: Wang Nan , Wang Lixiang , Huang Chengcheng 
Published: October 2021

Abstract
Objective
Evidence linking total testosterone and bone mineral density (BMD) in adults is very limited. According to our review of the literature, only a few reports have focused on the relationship between total testosterone and bone mineral density in adults. Therefore, the purpose of this study was to determine the relationship between total testosterone and total bone mineral density in adults aged 40–60 years.

Methods
We used a cross-sectional study of a non-institutionalized U.S. population sample from the National Health and Nutrition Examination Survey. A weighted multivariate linear regression model was used to evaluate the relationship between total testosterone and total bone mineral density. Subgroup analyses were further performed.

Results
In multiple regression models adjusted for potential confounders, total testosterone levels were inversely associated with total bone mineral density. However, in the sex-stratified subgroup analysis, the association between total testosterone levels and total bone mineral density was not significant in female adolescents. There was no negative association between total testosterone and total BMD among men, adults 40 to 60 years of age, and other racial/ethnic groups. There is a negative association between total testosterone and total bone mineral density when total testosterone concentration is greater than 500 ng/dL among Non-Hispanic black.

Conclusion
Our statistical results show that the association between total testosterone levels and total bone mineral density varies by gender and race. Elevated total testosterone levels below 500 ng/dL have adverse effects on bone health. Total testosterone concentrations below 500 ng/dL may have no effect on bone health.
Adipogenic differentiation was inhibited by downregulation of PPARγ signaling pathway in aging tendon stem/progenitor cells
Authors: Lai Fan , Wang Jingjing , Tang Hong , Bian Xuting , Lu Kang , He Gang , Huang Pan , Liu Juan , Zhou Mei , Liu Jian , Tao Xu , Tang Kang-lai 
Published: October 2021

Abstract
Background
Tendon stem/progenitor cells (TSPCs) play a vital role in tendon repair and regeneration. Previously we found more adipocytes accumulated in the patellar tendon injury sites in aging rats compared with the young ones, of which the mechanism is still unknown. Here, we want to identify whether erroneous differentiation of TSPCs by aging accounts for the adipocyte accumulation.

Methods
TSPCs from young and aging rats were isolated and propagated. Both young and aging TSPCs were induced to differentiate into adipocytes, and Oil red O staining, quantitative real-time polymerase chain reaction (qRT-PCR), western-blot and immunofluorescent staining were used to evaluate the capability of TSPCs. RNA sequencing was utilized to screen out different genes and signaling pathways related to adipogenesis between young and aging TSPCs.

Results
The Oil red O staining showed there were more adipocytes formed in young TSPCs. Besides, adipogenic markers perilipin, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding proteins alpha (C/EBPα) and Fatty acid-binding protein 4 (FABP4) were elevated both at gene and protein level. PPARγ signaling pathway was selected as our target via RNA sequencing. After adding the signaling activators, Rosiglitazone maleate (RM), inhibited adipogenesis of aging TSCs was reversed.

Conclusions
In conclusion, aging inhibited adipogenesis of TSPCs by down‐regulating PPARγ signaling. It is not likely that the adipocyte accumulation in aging tendon during repair was due to the aging of TSPCs. This may provide new targets for curing aging tendon injuries or tendinopathies.
MiR-4303 relieves chondrocyte inflammation by targeting ASPN in osteoarthritis
Authors: Wang Chunyu , Wang Li , Guan Xingfa , Yue Changfeng 
Published: October 2021

Abstract
Background
Osteoarthritis (OA) is a severe articular cartilage disease whose pathogenesis involves the inflammation of chondrocytes. MicroRNAs (miRNAs) are considered to be effective inflammation regulators. However, the regulatory mechanism of miRNAs in osteoarthritis needs to be further elucidated. In this paper, we aim to investigate the underlying mechanisms by which miR-4303 regulates osteoarthritis.

Methods
RT-qPCR is performed to detect the mRNA expression levels of miR-4303, ASPN, PDIA3, PIK3CA, and TRAF3. CCK-8 assay and EdU assay are carried to assess chondrocyte viability. The protein expression levels of ASPN, PCNA, Ki-67, CyclinA1, CyclinB1, CyclinD2, p27, Bax, Bcl-2, cleaved caspase-3, and Cleaved caspase-9 were measured by western blot. FACs is performed to detect the cell cycle and apoptosis of chondrocyte. ELISA is conducted to assess the levels of TNF-β, IL-1β and IL-6 in the supernatant of chondrocytes. The potential binding sites of miR-4303 and ASPN are predicted by the miRDB database and confirmed by the dual-luciferase reporter gene assay.

Results
Our findings illustrated that miR-4303 was down-regulated in arthritic tissues and LPS-induced chondrocytes; miR-4303 overexpression rescued the decrease in cell viability, cell cycle arrest and apoptosis induced by LPS. Furthermore, miR-4303 overexpression inhibited the release of inflammatory factors in LPS-induced chondrocytes, miR-4303 relieved chondrocyte inflammation via targeting ASPN.

Conclusion
MiR-4303 serves as a prognostic biomarker and relieves chondrocyte inflammation via targeting ASPN. Our findings provide novel prognostic biomarkers in predicting the progression and prognosis of osteoarthritis.
LIPUS inhibits inflammation and catabolism through the NF‐κB pathway in human degenerative nucleus pulposus cells
Authors: Yi Weiwei , Chen Qing , Liu Chuan , Li Kaiting , Tao Bailong , Tian Guihua , Zhou Lu , Li Xiaohong , Shen Jieliang , Liu Bo , Hu Zhenming , Wang Dawu , Bai Dingqun 
Published: October 2021

Abstract
Background
Low-intensity pulsed ultrasound (LIPUS) is a safe and noninvasive rehabilitative physical therapy with anti-inflammatory effects. The current study investigated the effect of LIPUS on the inflammation of nucleus pulposus (NP) cells and its underlying mechanism.

Methods
Human NP cells were acquired from lumbar disc herniation tissue samples and cultured for experiments. Human NP cells were treated with LPS and then exposed to LIPUS (15 mW/cm2, 30 mW/cm2 and 60 mW/cm2) for 20 min daily for 3 days to determine the appropriate intensity to inhibit the expression of the inflammatory factors TNF-α and IL-1β. The gene and protein expression of aggrecan, collagen II, MMP-3 and MMP-9 was measured by real‐time PCR and western blotting, respectively. The activity of the nuclear factor‐kappa B (NF‐κB) pathway was examined by western blotting and immunofluorescence. After pretreatment with the NF-κB inhibitor PDTC, the expression of TNF-α, IL-1β, MMP-3 and MMP-9 was measured by real‐time PCR.

Results
LIPUS at intensities of 15 mW/cm2, 30 mW/cm2 and 60 mW/cm2 inhibited LPS-induced NP cell expression of the inflammatory factors TNF-α and IL-1β, especially at 30 mW/cm2. LIPUS significantly upregulated the gene and protein expression of aggrecan and collagen II and downregulated the gene and protein expression of MMP-3 and MMP-9 in LPS-induced NP cells. The NF‐κB signaling pathway was inhibited by LIPUS through inhibiting the protein expression of p-P65 and the translocation of P65 into the nucleus in LPS-induced NP cells. In addition, LIPUS had similar effects as the NF-κB inhibitor PDTC by inhibiting the NF-κB signaling pathway, inflammation and catabolism in LPS-induced human degenerative nucleus pulposus cells.

Conclusion
LIPUS inhibited inflammation and catabolism through the NF‐κB pathway in human degenerative nucleus pulposus cells.
Three-dimensional morphological study of the proximal femur in Crowe type IV developmental dysplasia of the hip
Authors: Yang Yuhui , Liao Weihong , Yi Weiqun , Jiang Hai , Fu Guangtao , Ma Yuanchen , Zheng Qiujian 
Published: October 2021

AbstractBackgroundWhen performing femoral reconstruction in patients with Crowe type IV developmental dysplasia of the hip (DDH), anatomical deformity presents many technical challenges to orthopedic surgeons. The false acetabulum is suggested to influence load transmission and femoral development. The aim of this study was to describe the morphological features of dysplastic femurs in Crowe type IV DDH and further evaluate the potential effect of the false acetabulum on morphological features and medullary canal of Crowe type IV femurs.MethodsWe analyzed preoperative computed tomography scans from 45 patients with 51 hips (25 hips without false acetabulum in the IVa group and 26 hips with false acetabulum in the IVb group) who were diagnosed with Crowe type IV DDH and 30 normal hips in our hospital between January 2009 and January 2019. Three-dimensional reconstruction was performed using Mimics software, and the coronal femoral plane was determined to evaluate the following parameters: dislocation height, dislocation ratio, height of the femoral head (FH), height of the greater trochanter (GT), GT–FH height discrepancy, height of the isthmus, neck-shaft angle, femoral offset and anteversion of the femoral neck. The mediolateral (ML) width, anterolateral (AP) width and diameter of medullary canal of the proximal femur were measured on the axial sections. Further, canal flare index (CFI), metaphyseal-CFI and diaphyseal-CFI were also calculated.ResultsCompared with the normal femurs, the Crowe type IV DDH femurs had a higher femoral head, larger GT–FH height discrepancy, larger femoral neck anteversion, higher isthmus position and smaller femoral offset. Dislocation height and dislocation rate were significantly larger in the IVa DDH group (65.34 ± 9.83 mm vs. 52.24 ± 11.42 mm). Further, the IVb femurs had a significantly lower isthmus position, larger neck-shaft angle and smaller femoral neck anteversion than IVa femurs. The ML, AP canal widths and the diameter of medullary canal in both DDH groups were significantly smaller than the normal group. Dimensional parameters of IVa femurs were also narrower than IVb femurs in most sections, but with no difference at the level of isthmus. According to the CFIs, the variation of proximal medullary canal in IVb femurs was mainly located in the diaphyseal region, while that in IVa femurs was located in the whole proximal femur.ConclusionsHigh dislocated femurs are associated with more anteverted femoral neck, smaller femoral offset and narrower medullary canal. Without stimulation of the false acetabulum, IVa DDH femurs were associated with higher dislocation and notably narrower medullary canal, whose variation of medullary canal was located in the whole proximal femur.
Multiple bronchiolar adenomas with malignant transformation and CCNE1 mutation: a case report and literature review
Authors: Li Xiaojun , Wu Yonghui , Hui Dayang , Luo Xiaoxuan , Wu Weibin , Zhang Jian , Chen Huiguo 
Published: October 2021

Abstract
Background
Bronchiolar adenoma (BA) is a recently proposed diagnostic terminology, which is considered as the expansion of the concept of ciliated muconodular papillary tumors. BA is considered to be a benign neoplasm, but a few previous cases have been reported with the possibility of malignant transformation. Therefore, the genetic and histological nature of BA is controversial so far. We describe a rare case of multiple BAs with malignant transformation and CCNE1 (cyclin E1) mutation to increase the understanding of this disease.

Case description
A 56-year-old woman was admitted to our hospital due to two ground-glass nodules (GGNs) in the left lung detected by chest CT without symptom. The pure GGN located in the upper lingual segment about 6 mm in diameter and another mixed GGN located in the dorsal segment about 7 mm. The two GGNs have been found a year ago without treatment, and the mixed GGN become larger to 8 mm with vacuole sign in the next year health checkup. We performed a wedge resection of the two nodules completely by video-assisted thoracoscopy (VATS). Postoperative pathology indicated that the pure GGN was atypical bronchial adenoma, while the mixed GGN was atypical bronchial adenoma with malignant transformation which was missed in frozen section. Gene mutations analysis by next-generation sequencing (NGS) showed CCNE1 gene mutation in both lesions, and her-2 mutation was identified in the mixed GGN. The programmed cell death 1 ligand 1 (PD-L1) expression analysis of tumor cells showed 0% and less than 1% in the pure GGN and the mixed GGN, respectively.

Conclusion
BA is generally considered to be a benign tumor. The present study indicated that BA may be carcinogenic in atypical cases with some driver genes mutation and we should be vigilant for its potentiality of malignant transformation in clinical practice.
Scutellarin ameliorates neonatal hypoxic-ischemic encephalopathy associated with GAP43-dependent signaling pathway
Authors: Niu Rui-Ze , Xiong Liu-Lin , Zhou Hao-Li , Xue Lu-Lu , Xia Qing-Jie , Ma Zheng , Jin Yuan , Chen Li , Jiang Ya , Wang Ting-Hua , Liu Jia 
Published: October 2021

AbstractBackgroundNeonatal hypoxic-ischemic encephalopathy (HIE) refers to the perinatal asphyxia caused by the cerebral hypoxic-ischemic injury. The current study was aimed at investigating the therapeutic efficacy of Scutellarin (Scu) administration on neurological impairments induced by hypoxic-ischemic injury and exploring the underlying mechanisms.MethodsPrimary cortical neurons were cultured and subjected to oxygen–glucose deprivation (OGD), and then treated with Scu administration. The growth status of neurons was observed by immunofluorescence staining of TUJ1 and TUNEL. Besides, the mRNA level of growth-associated protein 43 (GAP43) in OGD neurons with Scu treatment was detected by quantitative real-time polymerase chain reaction (qRT-PCR). To further verify the role of GAP43 in Scu treatment, GAP43 siRNA and knockout were applied in vitro and in vivo. Moreover, behavioral evaluations were performed to elucidate the function of GAP43 in the Scu-ameliorated long-term neurological impairments caused by HI insult. The underlying biological mechanism of Scu treatment was further elucidated via network pharmacological analysis. Finally, the interactive genes with GAP43 were identified by Gene MANIA and further validated by qRT-PCR.ResultsOur data demonstrated that Scu treatment increased the number of neurons and axon growth, and suppressed cell apoptosis in vitro. And the expression of GAP43 was downregulated after OGD, but reversed by Scu administration. Besides, GAP43 silencing aggravated the Scu-ameliorated neuronal death and axonal damage. Meanwhile, GAP43 knockout enlarged brain infarct area and deteriorated the cognitive and motor dysfunctions of HI rats. Further, network pharmacological analysis revealed the drug targets of Scu participated in such biological processes as neuronal death and regulation of neuronal death, and apoptosis-related pathways. GAP43 exhibited close relationship with PTN, JAK2 and STAT3, and GAP43 silencing upregulated the levels of PTN, JAK2 and STAT3.ConclusionsCollectively, our findings revealed Scu treatment attenuated long-term neurological impairments after HI by suppressing neuronal death and enhancing neurite elongation through GAP43-dependent pathway. The crucial role of Scutellarin in neuroprotection provided a novel possible therapeutic agent for the treatment of neonatal HIE.Graphic abstract
Eat, breathe, sleep with Osteogenesis Imperfecta
Authors: LoMauro Antonella , Landoni Carlo Vittorio , Fraschini Paolo , Molteni Franco , Aliverti Andrea , Bertoli Simona , De Amicis Ramona 
Published: October 2021

Abstract
Background
Although Osteogenesis Imperfecta (OI) affects the connective tissue causing extremely brittle bones with consequent skeletal deformities, it is important to go beyond bones. Indeed, the quality of life in OI does not only depend on bones status, as OI might affect also other important functions. We have therefore implemented a multidisciplinary study to assess lung function, breathing pattern, sleep quality and nutritional status in 27 adult OI type III and IV patients (median age: 34.6 years; 19 women; 14 type III).

Results
According to nocturnal oxygen desaturation, two groups were identified: 13 patients with (OI_OSA, incidence: 48.2%) and 14 without (no_OSA) obstructive sleep apnea. The former was characterized by higher spinal and ribcage deformity, by more restrictive lung function, by paradoxical thoracic breathing in supine position, by rapid and shallow breathing, by higher body mass index, by longer neck and waist circumferences; by higher abdominal volume and by greater percentage of body fat mass, particularly localized in the trunk.
The best predictor of OI_OSA was the negative value of the supine ribcage contribution to tidal volume, followed by the ratio between the neck and the waist circumferences with body height and the supine thoraco-abdominal volumes phase shift angle.

Conclusions
The pathophysiology of OI ensued a dangerous vicious circle, in which breathing, sleep and nutritional status are tightly linked, and they might all end up in negatively affecting the quality of life. The vicious circle is fed by some intrinsic characteristics of the disease (thoracic, cranial and mandibular deformities) and some bad daily habits of the patients (i.e. physical inactivity and low dietary quality). The former impacts on restricting the respiratory function, the latter makes Olers more prone to experience overweight or obesity. The main consequence is a high incidence of obstructive sleep apnea, which remains an underdiagnosed disorder in individuals with severe OI who are obese, with a neck to height ratio over than 31.6%, and characterized by paradoxical breathing in supine position. A multidisciplinary approach, including evaluations of breathing, sleep and nutrition, is required to better manage the disease and fulfil the maximizing well-being of OI patients.
Impaired antioxidant KEAP1-NRF2 system in amyotrophic lateral sclerosis: NRF2 activation as a potential therapeutic strategy
Authors: Bono Silvia , Feligioni Marco , Corbo Massimo 
Published: October 2021

Abstract
Background
Oxidative stress (OS) is an imbalance between oxidant and antioxidant species and, together with other numerous pathological mechanisms, leads to the degeneration and death of motor neurons (MNs) in amyotrophic lateral sclerosis (ALS).

Main body
Two of the main players in the molecular and cellular response to OS are NRF2, the transcription nuclear factor erythroid 2-related factor 2, and its principal negative regulator, KEAP1, Kelch-like ECH (erythroid cell-derived protein with CNC homology)-associated protein 1. Here we first provide an overview of the structural organization, regulation, and critical role of the KEAP1-NRF2 system in counteracting OS, with a focus on its alteration in ALS. We then examine several compounds capable of promoting NRF2 activity thereby inducing cytoprotective effects, and which are currently in different stages of clinical development for many pathologies, including neurodegenerative diseases.

Conclusions
Although challenges associated with some of these compounds remain, important advances have been made in the development of safer and more effective drugs that could actually represent a breakthrough for fatal degenerative diseases such as ALS.