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Αλέξανδρος Γ. Σφακιανάκης

Sunday, August 29, 2021

Astragaloside IV alleviates heart failure by regulating SUMO-specific protease 1

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Exp Ther Med. 2021 Oct;22(4):1076. doi: 10.3892/etm.2021.10510. Epub 2021 Jul 28.

ABSTRACT

The present study investigated whether the protective effect and mechanism of astragaloside IV (AS-IV) on heart failure (HF) involves small ubiquitin-like modifier (SUMO)-specific protease 1 (Senp1). Mouse HF was established by aortic constriction, inducing pressure overload. The model was confirmed by echocardiography 6 weeks after surgery. Mice were randomly divided into control, HF, HF+AS-IV, and AS-IV groups. Ventricular function was examined by echocardiography. Morphological changes of myocardial tissues were examined by H&E staining. The protein levels of the apoptosis-related proteins, cleaved caspase-3, caspase-3, Bcl2, Bax, and SUMO-Senp1 were determined by Western blotting. H2O2 in isolated mitochondria and cells was determined by Amplex Red. A reactive oxygen species (ROS) detection kit determined ROS levels in isolated mitochondria and HL-1 cells. JC-1 reagent measured mitochondrial membrane potential (ΔΨm). Apoptosis of HL-1 cells was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling. Compared with the control group, the heart weight and heart mass/body weight ratio increased in the HF group (P<0.05). Furthermore, the ejection fraction and left ventricular shortening fraction decreased (P<0.05), while the left ventricular end-diastolic diameter (LVID;d) and end-systolic diameter (LVID;s) increased (P<0.05). Finally, mitochondrial ROS and H2O2 increased (P<0.05), while the ΔΨm decreased (P<0.05). However, AS-IV improved the cardiac function of HF mice, decreased the level of ROS and H2O2 in the myocardium, suppressed the decrease in ΔΨm, and decreased the apoptosis of myocardial cells (P<0.05). AS-IV also decreased the Senp1-overexpression. Furthermore, in HL-1 cells, Senp1-overexpression signifi cantly inhibited the protective effects of AS-IV. AS-IV decreased oxidative stress in cardiomyocytes, decreased mitochondrial damage, inhibited ventricular remodeling, and ultimately improved cardiac function by inhibiting HF-induced Senp1-overexpression. This mechanism provides a novel theoretical basis and clinical treatment for HF.

PMID:34447469 | PMC:PMC8355636 | DOI:10.3892/etm.2021.10510

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Giant chondroid lipoma of the breast: A case report and literature review

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Exp Ther Med. 2021 Oct;22(4):1087. doi: 10.3892/etm.2021.10521. Epub 2021 Jul 30.

ABSTRACT

Chondroid lipoma is a rare benign lesion affecting the breast, in which the diagnosis of malignancy is difficult to be excluded during preoperative studies. In this respect, a correct histopathological diagnosis is mandatory in order to avoid overdiagnosis and subsequently overtreatment. In the present study, the case of a 61-year-old patient who self-referred for the development of a large tumor at the level of the left breast is reported. Biopsy raised the suspicion of a chondroid lipoma; thus, the patient was submitted to conservative surgery. The lesion was completely excised by performing a total mastectomy. The histopathological studies confirmed the presence of chondroid lipoma, with no signs of malignant transformation. At the 24-month follow-up interval no signs of recurrence were detected. In conclusion, although it may reach significan t dimensions, giant chondroid lipoma of the breast is a benign lesion that may benefit from conservative treatment and does not recur.

PMID:34447479 | PMC:PMC8355713 | DOI:10.3892/etm.2021.10521

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Fumaric acid and succinic acid treat gestational hypertension by downregulating the expression of KCNMB1 and TET1

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Exp Ther Med. 2021 Oct;22(4):1072. doi: 10.3892/etm.2021.10506. Epub 2021 Jul 28.

ABSTRACT

The present study hypothesized that fumaric acid and succinic acid may exhibit therapeutic effects on gestational hypertension. During pregnancy, estrogen upregulates ten-eleven translocation 1 (TET1) expression, which subsequently increases calcium-activated potassium channel subunit β1 (KCNMB1) expression. KCNMB1 is associated with hypertension. Fumaric acid and succinic acid are understood to inhibit TET. Therefore, the present study investigated whether fumaric acid and succinic acid exhibit therapeutic effects on gestational hypertension and whether these effects are mediated by TET1 and KCNMB1. Nω-Nitro-L-arginine methyl ester hydrochloride was injected into rats to establish a gestational hypertension model. Dimethyl fumarate (DMF) and succinic acid were administrated into rats to treat gestational hypertension. Rats were divided into fi ve groups: i) Control; ii) model; iii) DMF; iv) succinic acid; and v) DMF + succinic acid. Blood pressure was monitored by a noninvasive meter and urinary protein was determined using a urinary protein kit. Placenta pathology was examined by hematoxylin-eosin staining. Compared with the control group, urinary protein and blood pressure in the model group increased significantly. The placental cells in the control group were arranged orderly. However, in the model group, decidual cellular edema of placenta and vacuolar degeneration were observed, and the intervascular membrane was markedly thicker with plenty of fibrin deposition. These results indicate successful establishment of a gestational hypertension model. However, compared with the model group, urinary protein, blood pressure, edema, vacuoles and fibrin deposition were markedly reduced in the DMF, succinic acid and DMF + succinic acid groups. mRNA and protein levels of TET1 and KCNMB1 in placenta were evaluated by immunohist ochemical analysis, reverse transcription-quantitative polymerase chain reaction and western blotting. The TET1 and KCNMB1 levels in the model group were markedly increased compared with those in the control group. However, compared with the model group, the expression levels were markedly downregulated in the DMF, succinic acid and DMF + succinic acid groups. In conclusion, fumaric acid and succinic acid may treat gestational hypertension by downregulating the expression of KCNMB1 and TET1.

PMID:34447465 | PMC:PMC8355717 | DOI:10.3892/etm.2021.10506

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Behavioral Interventions Targeting Insufficient Upper Esophageal Sphincter Opening During Swallowing: A Scoping Review

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Dysphagia. 2021 Aug 26. doi: 10.1007/s00455-021-10349-6. Online ahead of print.

ABSTRACT

The upper esophageal sphincter (UES) plays a central role in safe swallowing. Impaired UES opening is commonly observed in individuals presenting with impaired swallowing and various interventions are available aiming to improve bolus passage across the UES during swallowing. This scoping review addressed the following question: Which behavioral interventions are available to improve UES opening for deglutition? We searched MEDLINE, CINAHL, Ovid Emcare, Web of Science, SCOPUS and ProQuest for studies that met the following criteria: i. behavioral interventions targeting UES opening ii. performed over a period of time, which iii. were assessed using UES specific outcome measures. Study quality was assessed using the Joanna Briggs Institute and GRADE frameworks. Data were extracted and synthesized into dominant themes. Of the 357 studies originally identified, 15 met inclusion criteria and reported interventions that were grouped into four intervention types: (1) floor of mouth exercises that were sub-categorized into the Shaker exercise and other strengthening exercises, (2) Mendelsohn maneuver, (3) lingual exercises and (4) mixed exercise paradigms. Across the included studies, varying levels of success in improving various aspects of UES opening metrics were reported. Nine of 15 studies evaluated patients with demonstrated swallowing impairment, whereas six studies evalua ted healthy adults. Quality assessment revealed significant variability in study quality, unclear reporting of participant training and treatment fidelity, as well as training dosage. The evidence base for the four behavioral intervention approaches targeting deglutitive UES opening is limited. The translation of existing evidence to clinical practice is hindered by small sample sizes and methodological limitations. Further research in this space is warranted.

PMID:34448028 | DOI:10.1007/s00455-021-10349-6

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Man with headache and altered mental status

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Emerg Med J. 2021 Jul;38(7):519-528. doi: 10.1136/emermed-2020-210071.

ABSTRACT

PresentationAn 83-year-old man presented for headache and altered mental status. Four days prior, he underwent endoscopic sinus surgery for nasal polyps. Over the two previous days, he gradually developed a headache and was brought to the emergency department when his wife noted mild confusion and generalised weakness. His examination was notable for a heart rate of 101 beats per minute, clear nasal discharge, meningismus and confusion to the date with generalised weakness. A lumbar puncture revealed cloudy cerebrospinal fluid (CSF) with a white blood cell count of 3519x10ˆ9/L (95% neutrophils). A CT scan of the head was obtained (figure 1).emermed;38/7/519/F1F1F1Figure 1Non-contrast CT scan of the head in axial plane. QUESTION: What is the appropriate next step in management?Obtain MRI of the brain to localise ischaemic damage.Administer broad-spectrum antibioti cs, including pseudomonal coverage.Consult otolaryngology to arrange functional endoscopic sinus surgery for CSF leak closure.Consult neurosurgery for surgical decompression of mass lesion(s).

PMID:34449420 | DOI:10.1136/emermed-2020-210071

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Dual laryngeal reinnervation in bilateral vocal fold paralysis: anatomical pitfalls

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Surg Radiol Anat. 2021 Aug 27. doi: 10.1007/s00276-021-02698-6. Online ahead of print.

ABSTRACT

BACKGROUND: Bilateral laryngeal reinnervation can be a promising procedure for reanimation of laryngeal muscles, but currently not yet standardized. Besides patient conditions some intraoperative anatomical pitfalls need to be solved.

METHODS: Twelve human head and neck specimens (24 sides) have been studied using microdissection and histological serial sections of the nerve s. The surgical anatomy of the dual reinnervation procedure according to JP Marie was investigated notably the branching pattern of the phrenic nerve (PN), the Ansa cervicalis (AC) and the recurrent laryngeal nerve (RLN).

RESULTS: Despite variations of the AC, a prominent inferior common trunk for sterno-hyoid and sterno-thyroid muscles can be used in more than 90% of the specimens. If the AC is missing because of previous surgery, the tiny nerve of the thyro-hyoid muscle can be used preferred. The PN display a double roots pattern from C3 to C4 cervical plexus in 50% of the specimens. A single root pattern can be found and an end-to-lateral neurorraphy can be used. Intra-laryngeal nerves pattern of the RLN display tiny collaterals which cannot be selected for abduction-adduction activity. Direct implantation of the Y-shape great auricular nerve within the posterior crico-arytenoid muscles can be a reliable method leading to challenging mechanical and functional conditions.

CONCLUSION: Several anatomical pitfalls, including intra-operative choices and variants of the donor nerves, but also the challenging intra-laryngeal dissection of the inferior laryngeal nerve need to be solved. A successful laryngeal reinnervation still needs further studies for a simplified procedure.

PMID:34453198 | DOI:10.1007/s00276-021-02698-6

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Additive Manufacturing for Personalized Skull Base Reconstruction in Endoscopic Transclival Surgery: A Proof of Concept

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World Neurosurg. 2021 Aug 24:S1878-8750(21)01256-0. doi: 10.1016/j.wneu.2021.08.080. Online ahead of print.

ABSTRACT

BACKGROUND: Endoscopic transnasal transclival intradural surgery is limited by a high postoperative cerebrospinal fluid leak rate.

OBJECTIVE: To investigate the role of 3D printing to create a personalized, rigid scaffold for clival reconstruction.

METHODS: Two different types of clivectomy were performed in 5 specimens, with the aid of neuronavigation, and 11 clival reconstructions were simulated. They were repaired with polylactide, 3D-printed scaffolds, manually designed in a computer-aided environment either on the real or the predicted defect. Scaffolds were printed with a fused filament fabrication technique and different offsets. They were positioned and fixed either following the gasket seal technique or with screws. Post-dissection radiological evaluation of scaffold position was performed in all cases. In three specimens, the CSF leak pressure point was measured immediately after reconstruction.

RESULTS: The production process took approximately 30 hours. The designed scaffolds were satisfactory when no offset was added. Wings were added during the design to allow for screw positioning, but broke in 30% of cases. Radiological assessment documented an extreme accuracy of scaffold positioning when the scaffold was created on the real defect; it was satisfactory when the predicted clivectomy was performed under neuronavigation guidance. The CSF leak pressure point was significantly higher when the scaffold was fixed with screws as compared to the gasket technique.

CONCLUSIONS: Additive manufacturing allows the creation of customized scaffolds that are effective, in this preclinical setting, in reconstructing even large and geometrically complex clival defects.

PMID:34450324 | DOI:10.1016/j.wneu.2021.08.080

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The potential of the incorporated collagen microspheres in alginate hydrogel as an engineered three-dimensional microenvironment to attenuate apoptosis in human pancreatic islets

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Via histochem

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Acta Histochem. 2021 Aug 24;123(7):151775. doi: 10.1016/j.acthis.2021.151775. Online ahead of print.

ABSTRACT

BACKGROUND: Tissue engineering is considered as a promising tool for remodeling the native cells microenvironment. In the present study, the effect of alginate hydrogel and collagen microspheres integrated with extracellular matrix components were evaluated in the decrement of apoptosis in human pancreatic islets.

MATERIALS/METHODS: For three-dimensional cultur e, the islets were encapsulated in collagen microspheres, containing laminin and collagen IV and embedded in alginate scaffold for one week. After that the islets were examined in terms of viability, apoptosis, genes and proteins expression including BAX, BCL2, active caspase-3, and insulin. Moreover, the islets function was evaluated through glucose-induced insulin and C-peptide secretion assay. In order to evaluate the structure of the scaffolds and the morphology of the pancreatic islets in three-dimensional microenvironments, we performed scanning electron microscopy.

RESULTS: Our findings showed that the designed hydrogel scaffolds significantly improved the islets viability using the reduction of activated caspase-3 and TUNEL positive cells.

CONCLUSIONS: The reconstruction of the destructed matrix with alginate hydrogels and collagen microspheres might be an effective step to promote the culture of the islets.

PMID:34450327 | DOI:10.1016/j.acthis.2021.151775

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BMP2 downregulates urokinase-type plasminogen activator via p38 MAPK: Implications in C2C12 cells myogenic differentiation

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Via histochem

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Acta Histochem. 2021 Aug 23;123(6):151774. doi: 10.1016/j.acthis.2021.151774. Online ahead of print.

ABSTRACT

Bone morphogenetic protein (BMP)2 strongly affects the differentiation program of myoblast cells by inhibiting myogenesis and inducing osteogenic differentiation. In turn, extracellular matrix (ECM) proteinases, such as urokinase-type plasminogen activator (uPA), can influence the fate of muscle stem cells by participating in ECM reorganization. Although both BMP2 an d uPA have antagonistic roles in muscles cells differentiation, no connection between them has been elucidated so far. This study aims to determine whether BMP2 regulates uPA expression in the myogenic C2C12 cell line and its impact on muscle cell fate differentiation. Our results showed that BMP2 did not modify C2C12 cell proliferation in a growth medium or myogenic differentiation medium. Although BMP2 inhibited myogenesis and induced osteogenesis, these effects were achieved with different doses of BMP2. Low concentrations of BMP2 blocked myogenesis, while a higher concentration was needed to induce osteogenesis. Reduced uPA expression was noticed alongside myogenic inhibition at low concentrations of BMP2. BMP2 activated p38 MAPK signaling to inhibit uPA activity. Furthermore, ectopic human uPA expression reduced BMP2's ability to inhibit the myogenic differentiation of C2C12 cells. In conclusion, BMP2 inhibits uPA expression through p38 MAPK and in vitro myogenesis at non-osteo genic concentrations, while uPA ectopic expression prevents BMP2 from inhibiting myogenesis in C2C12 cells.

PMID:34450502 | DOI:10.1016/j.acthis.2021.151774

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Catamnesis after a single intervention for tinnitus patients in a specialized clinic

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Via hno

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HNO. 2021 Aug 27. doi: 10.1007/s00106-021-01103-3. Online ahead of print.

ABSTRACT

BACKGROUND: Patients suffering from tinnitus require individualized clarification (counseling), sometimes going beyond the scope of the field of ENT and the initiation of specific interventions.

AIM: To investigate if patients who had a specific neurotological assessment including a psychosomatic medical history follow the recommendations provided to them. In addition, it should be exami ned whether compliance with the treatment suggestions has led to any psychological improvement in the suffering from tinnitus, evaluated by psychological tests.

MATERIAL AND METHOD: In295 out of 699 patients audiological tests were evaluated using the mini-questionnaire (TF 12) according to Hiller and Goebel and the German language version of the Hospitality Anxiety and Depression Scale (HADS) at 2 points in time with an interval of a least 6 months. The group of those who followed the recommendations were compared to the group of those who did not follow the recommendations.

RESULTS: A total of 180 patients (64.5%) followed at least 1 of the recommendations made to them. Patients who followed at least one recommendation benefited significantly more than the whole group in the TF 12 and in both HADS categories compared to the group that did not follow the recommendations.

CONCLUSION: In addition to counseling it was shown that the implementation of a specific measu re has a positive effect, detectable for the Progressive Muscle Relaxation (PMR). Specific for ENT, a hearing aid can initiate an improvement even if no statistically significant difference to the comparison group was found.

PMID:34453187 | DOI:10.1007/s00106-021-01103-3

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