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Πέμπτη 1 Ιουλίου 2021

Insulin growth factor-1 promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells through the Wnt/β-catenin pathway

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Exp Ther Med. 2021 Aug;22(2):891. doi: 10.3892/etm.2021.10323. Epub 2021 Jun 17.

ABSTRACT

Bone marrow mesenchymal stem cells (BMSCs) are stem cells that exist in bone marrow tissue and have osteogenic differentiation potential. Insulin growth factor-1 (IGF-1) plays a key role in the proliferation and osteogenic differentiation of BMSCs. However, the specific mechanism of IGF-1 in cell proliferation and osteogenic differentiation remains unclear. In the present study, BMSCs were transfected with lentivirus carrying the siRNA-Wnt3a gene, and the Wnt3a level in BMSCs was revealed to be reduced by western blotting, real-time quantitative polymerase chain reaction and immunofluorescence detection. Then, BMSCs were treated with 80 ng/ml IGF-1 in complete medium for 5 days. CCK-8 and cell cycle assays revealed that cell proliferation was significantly decreased in the siRNA-Wnt3a group than in the control group. The protein and mRNA levels of β-catenin and cyclin D1 were significantly downregulated in the siRNA-Wnt3a group compared with the control group. In addition, BMSCs were treated with IGF-1 in osteogenic differentiation medium for 7 and 21 days, and alkaline phosphatase staining and Alizarin Red staining demonstrated significantly reduced osteogenic differentiation ability in the siRNA-Wnt3a group compared with the control group. Furthermore, the protein and mRNA levels of β-catenin, RUNX2, and OPN were downregulated compared with the control group. Our findings revealed that IGF-1 promoted the proliferation and differentiation of BMSCs at least partially through the Wnt/β-catenin pathway. These findings provided new insight into the clinical treatment of bone disease.

PMID:34194569 | PMC:PMC8237273 | DOI:10.3892/etm.2021.10323

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Difluoromethylornithine attenuates isoproterenol-induced cardiac hypertrophy by regulating apoptosis, autophagy and the mitochondria-associated membranes pathway

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Exp Ther Med. 2021 Aug;22(2):870. doi: 10.3892/etm.2021.10302. Epub 2021 Jun 13.

ABSTRACT

Myocardial hypertrophy is an independent risk factor of cardiovascular diseases and is closely associated with the incidence of heart failure. In the present study, we hypothesized that difluoromethylornithine (DFMO) could attenuate cardiac hypertrophy through mitochondria-associated membranes (MAM) and autophagy. Cardiac hypertrophy was induced in male rats by intravenous administration of isoproterenol (ISO; 5 mg/kg/day) for 1, 3,7 and 14 days. For DFMO treatment group, rats were given ISO (5 mg/kg/day) for 14 days and 2% DFMO in their water for 4 weeks. The expression of atrial natriuretic peptide (ANP) mRNA,heart parameters, apoptosis rate, fibrotic area and protein expressions of cleaved caspase3/9, GRP75, Mfn2, CypD and VDAC1 were measured to confirm the development of cardiac hypertrophy, apoptosis and autophagy induced by ISO. ANP mRNA and MAM protein expression levels were assessed by reverse transcription-quantitative PCR and western blotting to evaluate hypertrophy and the effects of DFMO oral administration. The results demonstrated that heart parameters, ANP mRNA levels, fibrotic area and apoptosis rate were significantly increased in the heart tissue for ISO 7 and 14 day groups compared with the control group. Furthermore, treatment with DFMO significantly inhibited these indicators, and DFMO downregulated the MAM signaling pathway and upregulated the autophagy pathway in heart tissue compared with the ISO 14 day group. Overall, all ISO-induced changes analyzed in the present study were attenuated following treatment with DFMO. The findings form this study suggested that DFMO treatment may be considered as a potential strategy for preventing ISO-induced cardiac hypertrophy.

PMID:34194548 | PMC:PMC8237397 | DOI:10.3892/etm.2021.10302

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Vaginal birth after Cesarean experience in Romania: A retrospective case-series study and online survey

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Exp Ther Med. 2021 Aug;22(2):894. doi: 10.3892/etm.2021.10326. Epub 2021 Jun 18.

ABSTRACT

The high Romanian Cesarean delivery rates have led to an increase in a women's desire to achieve vaginal birth after Cesarean delivery (VBAC), but certain impediments make this process difficult. We retrospectively evaluated the VBAC cases in a tertiary maternity hospital from Romania, and assessed the Romanian women's opinion about VBAC using a questionnaire that was distributed to three specific Facebook groups. We evaluated 63 patients who achieved VBAC between January 2014 and August 2020. In addition, an online survey with 41 open and closed questions assessed the participants' opinion regarding VBAC in Romania. The results are summarized and discussed. The results revealed that VBAC rates were under 1%. The main observed complications that followed VBAC were postpartum hemorrhage (15.8%), and uterine atony (7.93%), while the most frequent ty pes of lesions encountered after VBAC were cervical tear (12.6%), followed by labial fissure (9.5%) and vaginal tear (7.9%). The patient's confidence in the health care system is low, and many women decide to try TOLAC at home. In conclusion, VBAC is an important topic in the context of high Romanian Cesarean rates, and the decision factors must provide consistent strategies that promote this mode of delivery.

PMID:34194570 | PMC:PMC8237270 | D OI:10.3892/etm.2021.10326

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Jianpiyiqi formula ameliorates chronic atrophic gastritis in rats by modulating the Wnt/β-catenin signaling pathway

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Exp Ther Med. 2021 Aug;22(2):878. doi: 10.3892/etm.2021.10310. Epub 2021 Jun 15.

ABSTRACT

Jianpiyiqi formula is a Traditional Chinese Medicine (TCM) prescription and is used for the clinical treatment of patients with chronic atrophic gastritis (CAG). The aim of the present study was to examine the underlying mechanisms of Jianpiyiqi formula treatment for CAG via the Wnt/β-catenin signaling pathway. The high-performance liquid chromatography (HPLC) chromatogram of Jianpiyiqi formula was constructed. A CAG rat model induced by N-methyl-N'-nitro-N-nitrosoguanidine and ranitidine was established. The body weight and food intake of the rats was recorded and rat gastric morphology was visually examined. Pathological analysis of rat gastric tissue was also performed. The levels of gastrin (GAS), pepsin (PP), somatostatin (SS) and prostaglandin E2 (PGE2) in rat serum were detected using ELISAs. The expression levels of proteins and genes associated with the Wnt/β-catenin signaling pathway were measured via immunohistochemistry and reverse transcription-quantitative PCR. The HPLC chromatogram of Jianpiyiqi formula was determined and as active components, liquiritin and hesperidin were identified from the chromatogram. Compared with the blank group, the body weight and feed intake of the rats were decreased, and gastric mucosal atrophy and inflammation appeared in the model group. Treatment with Jianpiyiqi formula increased the body weight and feed intake of the rats, as well as relieved the gastric atrophy and inflammation. The contents of GAS, PP, SS and PGE2 were significantly reduced in the model group compared with the blank group. Jianpiyiqi formula significantly increased GAS, PP, SS and PGE2 levels in serum of rats with CAG. In the model group, Wnt1, β-catenin and cyclin D1 protein expression levels were increased, and glycogen synthase kinase-3β (GSK-3β) protein ex pression levels were decreased. Jianpiyiqi formula decreased the protein expression levels of Wnt1, β-catenin and cyclin D1 and increased the protein expression levels of GSK-3β. Compared with the blank group, the mRNA expression levels of Wnt1, Wnt5a, β-catenin, cyclin D1 and MMP7 were upregulated, and the mRNA expression levels of GSK-3β were downregulated in the model group. Treatment with Jianpiyiqi formula downregulated the mRNA expression levels of Wnt1, Wnt5a, β-catenin, cyclin D1 and MMP7 and upregulated the mRNA expression levels of GSK-3β. All of the experimental results indicated that Jianpiyiqi formula exerted a therapeutic effect on rats with CAG and inhibited the activation of the Wnt/β-catenin signaling pathway. Thus, Jianpiyiqi formula, as an effective TCM prescription for treating patients with CAG, may be more widely used in the clinic.

PMID:34194556 | PMC:PMC8237394 | DOI:10.3892/etm.2021.10310

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Office-based phonosurgery

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Via hno

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HNO. 2021 Jun 30. doi: 10.1007/s00106-021-01081-6. Online ahead of print.

ABSTRACT

Significant and new impulses regarding the treatment concept for outpatient phonosurgery on unsedated patients are currently coming from various Anglo-American authors. These "office-based procedures" have been propagated as an alternative to many conventional surgical interventions under anesthesia. The main reason for this remarkable development is the use of new endoscopic techniques in com bination with photoangiolytic laser (KTP and blue laser), which allow safe and efficient phonosurgical procedures. Patient acceptance is high since outpatient procedures are considered to have a lower surgical risk. Despite the widespread euphoria, there is a lack of studies evaluating the medical decision criteria and safety management of office-based laryngeal surgery.

PMID:34195859 | DOI:10.1007/s00106-021-01081-6

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Morphological features of the chiasma tendinum and its relation with surface landmarks and pulleys: a cadaveric study

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Surg Radiol Anat. 2021 Jul 1. doi: 10.1007/s00276-021-02783-w. Online ahead of print.

ABSTRACT

AIM: Chiasma tendinum (Camper's chiasm) is of great importance in the delicate movements and stability of the fingers and takes place poorly in the literature. This study aims to reveal the morphometric details of the chiasma tendinum in relation with pulleys and other relevant structures.

MATERIALS AND METHODS: Palm and 2nd to 5th fingers of 10 (6 male, 4 female) formalin fi xed cadavers were used bilaterally. After determining the superficial reference points on the fingers, the skin and the tendon sheath were incised, and then measurements of chiasma tendinum and related tendons were performed. The measurements were analyzed with respect to fingers, genders, and sides. Finally, the types of chiasma tendinum were identified and then grouped as symmetrical, asymmetrical, and pseudo chiasm.

RESULTS: Pulley and chiasma tendinum positions were correlated with finger length (p < 0.01). Pulley lengths were significantly less in females. Asymmetrical chiasma tendinum types were found in 45% of the fingers. In most comparisons, values for fifth finger were significantly different than that of other fingers and chiasma tendinum types differed according to fingers and gender. The case of no fiber exchange was observed only in the 5th finger in 15%.

CONCLUSION: Findings related to the prediction of location of the pulleys and chiasma tendinum accor ding to the superficial signs, awareness of cases where one of the two arms of the flexor digitorum superficialis is extremely thin and no fiber exchanges that may be risk factors for spontaneous tendon rupture may help provide more accurate approaches in relevant clinical applications.

PMID:34196774 | DOI:10.1007/s00276-021-02783-w

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Management and outcome of vagus nerve stimulator implantation: experience of an otolaryngeal/neuropediatric cooperation

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Eur Arch Otorhinolaryngol. 2021 Jul 1. doi: 10.1007/s00405-021-06943-x. Online ahead of print.

ABSTRACT

OBJECTIVE: Vagus nerve stimulator (VNS) implantation is an established therapy for pharmacoresistant epilepsy that is not amenable to curative epilepsy surgery. Historically, VNS implantation has been performed by neurosurgeons, but otolaryngologist involvement is increasingly common. In this retrospective study, we aimed to evaluate the efficacy and safety of VNS implantation in children and adolescents from the otolaryngologists' perspective.

METHODS: This study included children and adolescents who had undergone VNS implantation at the study center between 2014 and 2018. Patient files were analyzed with regards to the durations of device implantation and hospitalization, postoperative complications, and clinical outcome, including seizure frequency, clinical global impression of improvement (CGI-I) score, and quality of life (QoL).

RESULTS: A total of 73 children underwent VNS surgery. The median age at implantation was 9.3 ± 4.6 years, and median epilepsy duration before VNS surgery was 6 ± 4 years. Lennox-Gastaut syndrome was the most common syndrome diagnosis (62.3%), and structural abnormalities (49.3%) the most frequent etiology. Operation times ranged from 30 to 200 min, and median postoperative hospitalization length was 2 ± 0.9 days. No complications occurred, except for four revisions and two explantations due to local infections (2.7%). Among our patients, 76.7% were responders (≥ 50% reduction in seizure frequency), 72.1% showed improved CGI-I scores, and 18.6-60.5% exhibited considerable improvements in the QoL categories energy, emotional health, and cognitive functions.

CONCLUSION: Our results indicate that VNS implantation is a highly effective and safe treatment option for children and adolescents with AED-refractory epilepsies who are not candidates for curative epilep sy surgery.

PMID:34196736 | DOI:10.1007/s00405-021-06943-x

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Suprameatal-transzygomatic root endoscopic approach to the geniculate ganglion: an anatomical and radiological study

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Eur Arch Otorhinolaryngol. 2021 Jul 1. doi: 10.1007/s00405-021-06965-5. Online ahead of print.

ABSTRACT

PURPOSE: To describe the suprameatal-transzygomatic root endoscopic approach (STEA) to the geniculate ganglion (GG), the labyrinthine facial nerve (FN) and epitympanum.

METHODS: The feasibility and limits of the STEA, maintaining the integrity of the ossicular chain, were analysed. Ten human cadaveric ears were dissected. Step-by-step description of the technique and relevant measurements were taken during the approach. The visualization and surgical working field on the anterior and posterior medial epitympanum, GG, greater superficial petrosal nerve, the labyrinthine FN and suprageniculate area were evaluated. The range of motion through the approach and the rate of the decompression of the GG and the labyrinthine portion of the FN were assessed as well. CT-scan measurements were compared with those obtained during the dissec tion.

RESULTS: A complete exploration of the epitympanum was possible in every specimen. Decompression of the GG and first portion of the FN was achieved without any trauma to the ossicular chain in nine ears. The endoscope movements were mainly limited by the distance between bony buttress-short process of the incus-tegmen. The working space, during GG and labyrinthine FN decompression, was limited by the distance between malleus head-medial epitympanic wall and malleus head-GG. Radiologic measurements were consistent with those obtained during the dissections.

CONCLUSION: The STEA is a promising minimally invasive approach for decompression of the GG and FN's labyrinthine portion. The applications of this corridor include the exploration and surgery of the medial epitympanum, preserving the ossicular chain.

PMID:34196734 | DOI:10.1007/s00405-021-06965-5

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Clinical evaluation of antibiotic regimens in patients with surgically verified parapharyngeal abscess: a prospective observational study

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Eur Arch Otorhinolaryngol. 2021 Jul 1. doi: 10.1007/s00405-021-06962-8. Online ahead of print.

ABSTRACT

PURPOSE: We aimed to evaluate the effectiveness of different antibiotic regimens for the treatment of parapharyngeal abscess (PPA) and characterize patients, who suffered potentially preventable complications (defined as death, abscess recurrence, spread of infection, or altered antibiotic treatment because of insufficient progress).

METHODS: Sixty adult patients with surgically verified PPA were prospectively enrolled at five Danish Ear-nose-throat departments.

RESULTS: Surgical treatment included internal incision (100%), external incision (13%), and tonsillectomy (88%). Patients were treated with penicillin G ± metronidazole (n = 39), cefuroxime ± metronidazole (n = 16), or other antibiotics (n = 5). Compared to penicillin-treated patients, cefuroxime-treated patients were hospitalized for longer (4.5 vs 3.0 days, p = 0.007), were more frequently admitted to intensive care (56 vs 15%, p = 0.006), underwent external incision more frequently (31 vs 5%, p = 0.018), and suffered more complications (50 vs 18%, p = 0.022), including re-operation because of abscess recurrence (44 vs 3%, p < 0.001). Nine patients suffered potentially preventable complications. These patients displayed significantly higher C-reactive protein levels, received antibiotics prior to admission more frequently, underwent external incision more commonly, and were admitted to intensive care more frequently compared to other patients.

CONCLUSION: The majority of patients with PPA were effectively managed by abscess incision, tonsillectomy, and penicillin G ± metronidazole. Cefuroxime-treated patients were more severely ill at time of admission and had worse outcome compared to penicillin-treated patients. We recommend penicillin G + metronidazole as standard treatment for patients with PPA, but in cases with more risk factors for potentially preventable complications, we recommend aggressive surgical and broadened antibiotic therapy, e.g. piperacillin-tazobactam.

PMID:34196735 | DOI:10.1007/s00405-021-06962-8

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Τετάρτη 30 Ιουνίου 2021

Location, location, location: Melanoma cells “living at the edge”

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Abstract

Abnormal cell migration and invasion underlie metastatic dissemination, one of the major challenges for cancer treatment. Melanoma is one the deadliest and most aggressive forms of skin cancer due in part to its migratory and metastatic potential. Cancer cells use a variety of migratory strategies regulated by cytoskeletal remodelling. In particular, we discuss the importance of amoeboid invasive melanoma strategies, since they have been identified at the edge of human melanomas. We hypothesize that the presence of amoeboid melanoma cells will favour tumour progression since they are invasive and metastatic; they support immunosuppression; they harbour cancer stem cell properties and they are involved in therapy resistance. The Rho-ROCK-Myosin II pathway is key to maintain amoeboid melanoma invasion but this pathway is further regulated by pro-tumorigenic/pro-metastatic/pro-survival signalling pathways such as JAK-STAT3, TGFβ-SMAD, NF-κB, Wnt11/5-FDZ7 and BRAFV600E-ME K-ERK. These pathways support amoeboid behaviour and are actionable in the clinic. After melanoma wide surgical margin removal, we propose that possible remaining melanoma cells should be eradicated using anti-amoeboid therapies.

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