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Αλέξανδρος Γ. Σφακιανάκης

Monday, January 24, 2022

The muscular branching patterns of the ulnar nerve in fetal forearms

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Surg Radiol Anat. 2022 Jan 23. doi: 10.1007/s00276-021-02870-y. Online ahead of print.

ABSTRACT

OBJECTIVE: We aimed to present our findings systematically by examining the muscular branching patterns of the ulnar nerve (UN) in the forearms of fetuses.

METHODS: This study was conducted on the 52 forearms of 26 formalin-fixed fetal cadavers with gestational ages varying between 19 and 37 weeks. The anatomical dissection was performed by using stereomicroscope with × 8 m agnification. The numbers of muscular branches leaving UN and their order of leaving main nerve were noted down. The findings were classified according to the muscles they reached, and branching typing was done.

RESULTS: It was found that a total of 2-6 muscular branches left UN to reach flexor carpi ulnaris (FCU) and flexor digitorum profundus (FDP). UN was classified by separating into five main types according to the number of muscular branches, and these types were classified into 16 different branching patterns according to the order of branches leaving from the main trunk and going to FCU and FDP. The pattern where two branches left UN was classified as Type I (n = 6), three branches left was classified as Type II (n = 18), four branches left was classified as Type III (n = 24), five branches left was classified as Type IV (n = 3), and six branches left was classified as Type V (n = 1). Martin-Gruber connection occurred in 17 (32.7%) fetal forearms.

CONCLUSION: We believe that the information that UN can demonstrate different branching patterns on the forearm can help the surgeons to prevent complications that may develop in potential nerve injury during the selection and transfer of relevant branch.

PMID:35066639 | DOI:10.1007/s00276-021-02870-y

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Synergistic effect of Bruton's tyrosine kinase and TNF-α in the regulation of rheumatoid arthritis and underlying mechanisms

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Exp Ther Med. 2022 Feb;23(2):141. doi: 10.3892/etm.2021.11064. Epub 2021 Dec 14.

ABSTRACT

The presence of Bruton's tyrosine kinase (BTK) in macrophages has been recommended as a promising therapeutic target for rheumatoid arthritis (RA). In addition, activated macrophages in the inflamed joints of patients with RA can also produce a plethora of cytokines, such as TNF-α. The aim of the present study was to investigate the potential role of BTK and TNF-α in the regulation of RA. The results demonstrated that higher levels of BTK and TNF-α were observed in macrophages in inflamed RA joints compared with those in normal joint tissues. Subsequently, the role of BTK and TNF-α in the regulation of cellular process in inflammatory macrophages was analyzed. It was demonstrated that aberrant expression of BTK and TNF-α in inflammatory macrophages can lead to higher cell proliferation rates. Once the expression of BTK or TNF-α was restricte d by using short interfering (si)RNAs (siBTK or siTNF-α), the activity of inflammatory macrophages was significantly downregulated. Of note, when the expression of BTK and TNF-α was simultaneously decreased, the proliferation rate of inflammatory macrophages was inhibited to the greatest extent. Subsequently, the underlying mechanisms through which BTK and TNF-α can regulate RA were investigated. The results demonstrated that BTK mainly regulated the ERK/JNK pathway, while TNF-α mainly affected the inactive rhomboid protein 2/B-cell-activating factor pathway. Finally, animal experiments demonstrated that simultaneous silencing of both BTK and TNF-α can significantly alleviate the symptoms associated with RA.

PMID:35069822 | PMC:PMC8756421 | DOI:10.3892/etm.2021.11064

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MicroRNA-195-5p inhibits the progression of hemangioma via targeting SKI

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Exp Ther Med. 2022 Feb;23(2):165. doi: 10.3892/etm.2021.11088. Epub 2021 Dec 22.

ABSTRACT

Hemangioma (HA), which is characterized by aberrant endothelial cell proliferation in blood vessels, is a common tumor during infancy. MicroRNAs (miRNAs/miRs) collectively participate in the development of HA; however, the potential roles of miR-195-5p in HA are not completely understood. The aim of the present study was to investigate the roles of miR-195-5p in HA. In the present study, miR-195-5p was found to be downregulated in HA cells, such as the XPTS-1 human infantile hemangioma-derived endothelial cell line and the EOMA hemangioendothelioma cell line. Overexpression of miR-195-5p was shown to suppress HA cell viability, colony formation and proliferation, and induced HA cell apoptosis. Furthermore, miR-195-5p downregulated Bcl-2 expression and upregulated Bax and Bcl-2 expression levels. V-ski sarcoma viral oncogene homolog (SKI) was ident ified as a target of miR-195-5p. Co-transfection of miR-195-5p mimics and SKI 3'-untranslated region wild-type decreased HA cell luciferase activity. SKI overexpression alleviated the miR-195-5p-induced decrease in HA cell proliferation and increased HA cell apoptosis. In addition, the regulatory role of miR-195-5p on the expression of Bcl-2, Bax and poly(ADP-ribose) polymerase was reversed by SKI. Collectively, the results of the present study demonstrated that miR-195-5p suppressed HA progression and its effects were mediated via SKI. Therefore, the miR-195-5p/SKI axis may represent a novel therapeutic target for HA.

PMID:35069846 | PMC:PMC8753966 | DOI:10.3892/etm.2021.11088

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Mucosal gene expression profile of stricturing Crohn's disease: A preliminary study

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Exp Ther Med. 2022 Feb;23(2):149. doi: 10.3892/etm.2021.11072. Epub 2021 Dec 16.

ABSTRACT

Intestinal strictures are an important complication of Crohn's disease (CD), with ~40% of patients developing symptomatic obstruction within 10 years of diagnosis. However, there is a paucity of research examining the mechanisms driving the development of fibrotic strictures in CD. The present study aimed to identify the mucosal markers associated with stricturing complications by examining the differences in the gene expression profiles of two patient cohorts: Patients diagnosed with inflammatory CD (n=12) and patients with stricturing CD (n=9). For each patient, a paired sample of inflamed and uninflamed mucosa was isolated and assessed by quantitative PCR using a large panel of genes associated with inflammatory bowel disease. The presents study revealed a significantly increased level of four genes in the mucosa of patients with strictures com pared with the inflammatory pattern of the disease: Formyl-peptide receptor 1 [P=0.019; fold change (FC)=11.6], C-C chemokine receptor type 1 (P=0.035; FC=5.44), IFN-γ-inducible protein 10 (P=0.037; FC=3.8) and C-C chemokine ligand 25 (P=0.048; FC=3.56). The augmented expression of these four genes in the CD stricturing phenotype, if confirmed in larger cohorts of patients, could help elucidate the mechanisms leading to disease-associated complications.

PMID:35069830 | PMC:P MC8756406 | DOI:10.3892/etm.2021.11072

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Effect of Src tyrosine kinase on a rat model of asthma

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Exp Ther Med. 2022 Feb;23(2):172. doi: 10.3892/etm.2021.11095. Epub 2021 Dec 27.

ABSTRACT

Src tyrosine kinase is a protein encoded by the Src gene. The present study aimed to determine the role of Src protein kinase in asthma using small interfering RNA (siRNA) technology. Several Src siRNAs were designed and the most effective siRNA pair was selected. A rat model of asthma was established using ovalbumin, and the rats were treated with Src siRNA, empty vector or phosphate-buffered saline (PBS). A non-asthmatic control group was also established. The rats were clinically observed and Src mRNA and protein levels were measured by reverse transcription-quantitative PCR and western blot analysis, respectively. Pathological observation of the lung tissue, counting of white blood cells (WBCs) and eosinophils (EOSs) and analysis of the concentrations of IL-5, IL-33 and IFN-γ in the bronchoalveolar lavage fluid were performed. The expression levels of Src mRNA in the control, PBS, empty vector and siRNA groups were 110±30.7x103, 253±55.4x103, 254±41.3x103 and 180±50.9x103, respectively. Histochemical analysis of the lung tissue of rats in the siRNA group exhibited a relatively complete lung structure and little damage to the alveolar cavity. Src protein expression and IL-5, IL-33 levels, WBC and EOS levels were positively correlated with Src mRNA expression, while the IFN-γ concentration was negatively correlated with Src mRNA expression. These results indicate that Src knockdown inhibits the release of tracheal inflammatory factors and significantly alleviates asthma in rats. In conclusion, the present study utilized a gene transfer technique to interfere with the expression of Src in rats, which decreased the levels of IL-5, IL-33, WBCs and EOSs and increased the level of IFN-γ; these changes effectively ameliorated the condition of the trachea in asthmatic rats.

PMID:35069853 | PMC:PMC8764580 | DOI:10.3892/etm.2021.11095

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Lectin-type oxidized LDL receptor 1 modulates matrix metalloproteinase 2 production in peri-implantitis

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Exp Ther Med. 2022 Feb;23(2):171. doi: 10.3892/etm.2021.11094. Epub 2021 Dec 27.

ABSTRACT

Peri-implantitis is a disease in which inflammatory lesions that affect the surrounding soft and hard tissues develop. Matrix metalloproteinase 2 (MMP2) is hypothesized to be involved in this destructive process. However, the regulatory mechanism of action of MMP2 in the peripheral tissues of the implant are not fully understood. To determine the expression of MMP2 in peri-implantitis, peri-implant crevicular fluid (PICF) was collected from patients with peri-implantitis. The healthy volunteers' peripheral blood human macrophages infected with Porphyromonas gingivalis (P. gingivalis) were used as a cell model to explore the regulatory mechanism of MMP2 regarding dental implants. Western blotting, reverse transcription-quantitative PCR and immunofluorescence staining were used to measure the expression of MMP2 in the present study. MM P2 expression was increased in the PICF of the patients with peri-implantitis and in human macrophages infected with P. gingivalis. Lectin-type oxidized LDL receptor 1 (LOX-1) mediated the expression of MMP2 in human macrophages upon infection of P. gingivalis, whereas dendritic cell-associated c-type lectin-1 did not appear to be involved in this regulatory process. However, JNK and ERK1/2 were involved in P. gingivalis induced MMP2 expression. The results of this study showed that MMP2 was involved in peri-implantitis. MMP2 was upregulated by LOX-1 in a JNK and ERKk1/2 signaling dependent manner in the cell model. The LOX-1/MMP2 signaling pathway may thus be a potential target for management of peri-implantitis.

PMID:35069852 | PMC:PMC8764579 | DOI:10.3892/etm.2021.11094

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P2X7R antagonist protects against renal injury in mice with adriamycin nephropathy

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Exp Ther Med. 2022 Feb;23(2):161. doi: 10.3892/etm.2021.11084. Epub 2021 Dec 21.

ABSTRACT

Activation of the purinergic P2X7 receptor (P2X7R) has been associated with the development of experimental nephritis. Therefore, the current study aimed to explore the mechanism of P2X7R in renal injured mice with adriamycin (ADR) nephropathy. The protective effect of a P2X7R antagonist on the kidneys of mice with ADR nephropathy was also evaluated. Nephropathy was induced by a single intravenous injection of ADR (10.5 mg/kg). A total of 6 h before the model was established, the P2X7R antagonist A438079 (100, 200 and 300 µmol/kg) was injected into the mice, which was subsequently administered daily for 1 week by intraperitoneal injection. Subsequently, all mice were sacrificed, after which blood, 24 h-urine and the kidneys were collected. The levels of albumin (ALB) and total cholesterol (TC) in the serum, along with urine protein content at 24 h were determined using an automatic biochemical analyzer. The levels of IL-1β and IL-18 were additionally detected in the renal tissues by ELISA. Moreover, the expression of P2X7R, oxidized (ox)-low density lipoprotein (LDL), C-X-C motif chemokine ligand 16 (CXCL16), Bax, caspase-3 and NLRP3 in renal tissues was detected by immunohistochemistry. Apoptosis in the renal tissues was observed using the TUNEL assay. The results demonstrated that compared with the control group, decreased weight, increased proteinuria, decreased serum ALB and increased serum TC was observed in the ADR group. The expression of IL-1β, IL-18, P2X7R, ox-LDL, CXCL16, Bax, caspase-3 and NLRP3, as well as cellular apoptosis in the renal tissues of the ADR group, was significantly increased in the ADR group compared with the control. However, compared with the ADR group, the changes in all indices in the ADR + A438079 groups were attenuated. Overall, P2X7R, ox-LDL and CXCL16 may be associated with ADR nephropa thy, while inhibition of P2X7R may reduce the expression of ox-LDL by downregulating the CXCL16 pathway to alleviate kidney injury in mice with ADR nephropathy. Furthermore, activated P2X7R may promote the release of inflammatory cytokines IL-1β and IL-18 through the downstream P2X7R/NLRP3 pathway and upregulate the expression of Bax and caspase-3 to promote apoptosis, which participates in the process of ADR nephropathy. Inhibiting P2X7R may also reduce the release of IL-1β and IL-18 by downregulating the P2X7R/NLRP3 pathway, downregulating the expression of Bax and caspase-3, and reducing apoptosis, thereby alleviating kidney injury in mice with ADR nephropathy.

PMID:35069842 | PMC:PMC8753981 | DOI:10.3892/etm.2021.11084

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Therapeutic effect and mechanism of 4-phenyl butyric acid on renal ischemia-reperfusion injury in mice

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Exp Ther Med. 2022 Feb;23(2):144. doi: 10.3892/etm.2021.11067. Epub 2021 Dec 15.

ABSTRACT

The aim of the present study was to explore the effects and possible mechanism of 4-phenylbutyric acid (4-PBA) on renal ischemia-reperfusion injury (RIRI) in mice. A RIRI model of HK-2 cells was constructed using hypoxia/reoxygenation (H/R) treatment. Dexmedetomidine and 4-PBA were used to treat the cells before and after modeling. Apoptosis and expression levels of cyclophilin D (CypD), cytochrome c, eukaryotic translation initiation factor 2α (eIF2α), glucose-regulated protein 78 (GRP78), intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 were measured using flow cytometry, western blotting and immunohistochemistry. The renal volume, weight and renal arterial resistance index (RRI) were determined using the renal ischemia model. Compared with untreated model cells, 4-PBA treatment significantly decreased ap optosis and the expression levels of CypD, Cytochrome c, eIF2α and GRP78 in HK-2 cells. There was no significant change in renal volume and weight after modeling, but RRI was significantly decreased after 4-PBA treatments in the model. Western blotting and immunohistochemistry analysis demonstrated that 4-PBA treatment also significantly decreased the expression of ICAM-1 and VCAM-1. Overall, 4-PBA had a therapeutic effect on RIRI in mice. This protection may be mediated by decreasing the expression levels of CypD, Cytochrome c, eIF2α and GRP78, and subsequent reduction of cellular oxygen free radicals and apoptosis, leading to an alleviated endoplasmic reticulum stress response and RIRI.

PMID:35069825 | PMC:< a href="https://www.ncbi.nlm.nih.gov/pmc/PMC8756420/?utm_source=Inoreader&utm_medium=rss&utm_content=1ba2t84FK1dz-fAY5g7-lbp7yzA9oSsgU2XptRGyGkyx-wIkEA&ff=20220125000243&v=2.17.5" target="_blank" rel="noopener" class="underlink bluelink">PMC8756420 | DOI:10.3892/etm.2021.11067

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Electrochemical monitoring of bronchial inflammation in pediatric athletes: A prospective study

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Exp Ther Med. 2022 Feb;23(2):180. doi: 10.3892/etm.2021.11103. Epub 2021 Dec 28.

ABSTRACT

The assessment of inflammation by accessible, reproducible and especially non-invasive methods is one of the main goals for numerous medical specialties. One variable for assessment is the fraction of nitric oxide in exhaled air (FeNO), which correlates with the inflammatory syndrome of the airways. The objective of the present study was the biochemical evaluation of FeNO in children practicing sports in Oltenia, Romania. Between January and December 2018, children practicing sports (football, track and field, judo, fencing, handball, volleyball and basketball) were enrolled in the study. The FeNO values were compared with the asthma history and with the spirometric evaluation. A total of 23 children without a previous asthma diagnosis exhibited positive spirometry results. The prevalence of the disease was 3.6% in the cohort, and FeNO dosing show ed higher values in the group at risk in children diagnosed with asthma, compared with that in children without this diagnosis. The children who performed outdoor sports (soccer, and track and field) had higher electrochemical levels of nitric oxide compared with those who performed indoor sports (mean, 29.70 vs. 20.56; P<0.0005), which led to the hypothesis that these children had an increased risk of developing bronchospasm. FeNO dosing can thus be a useful and easy-to-use tool in practice for assessing bronchial inflammation in children practicing various types of sports. The spirometric data of undiagnosed asthma patients from the present study may indicate that the disease is still underdiagnosed within Romania.

PMID:3506 9861 | PMC:PMC8764892 | DOI:10.3892/etm.2021.11103

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Analysis of long-term anatomic results of radical mastoidectomy

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Exp Ther Med. 2022 Feb;23(2):156. doi: 10.3892/etm.2021.11079. Epub 2021 Dec 17.

ABSTRACT

A long-term, retrospective, non-controlled study was performed on the drainage results of mastoidectomy (both radical and modified radical) and the relevant statistical factors that could influence the anatomic outcome were defined. The present study took into consideration the same cohort of 200 patients we have communicated with before in our previous studies concerning the long-term functional results of mastoidectomy and long-term results of ossicular replacement with biovitroceramic prosthesis. The patients were clinically followed for the same period of 8.12 years. The drainage (anatomic) results, similar to previously published functional results, were defined by analytical function of the severity and the period of evolution of disease. The main goal was to define the situations and factors (presence of complications, type of disease, type of tympanic perforation or status of ossicular chain) that influenced the drainage results that could provide us with some type of anatomical prognosis. The follow-up started at the moment of complete epithelization for each cavity as time represents the main study comparison criteria. Drainage failure was assessed by the number of otorrhea episodes. It was concluded that practically and ideally, a maximum of 84% of the mastoid and petrous cells can be cleaned out. The results of 78% drainage success are congruent to this theory. The remaining 16% of cells may contain irreversible lesions.

PMID:35069837 | PMC:PMC8753967 | DOI:10.3892/etm.2021.11079

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