Αρχειοθήκη ιστολογίου

Δευτέρα 7 Φεβρουαρίου 2022

Wogonin reduces cardiomyocyte apoptosis from mitochondrial release of cytochrome c to improve doxorubicin-induced cardiotoxicity

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Exp Ther Med. 2022 Mar;23(3):205. doi: 10.3892/etm.2022.11128. Epub 2022 Jan 7.

ABSTRACT

Doxorubicin (DOX) has powerful anticancer properties, but its clinical application is affected by its serious cardiotoxicity. Wogonin (WG) has been shown to have marked cardiovascular protection potential. However, it is not known whether this potential can protect the heart from DOX damage. The aim of the present study was to investigate whether WG could ameliorate the cardiotoxicity of DOX. DOX and WG were used to establish a model of cardiac damage. Echocardiography, brain natriuretic peptide, creatine kinase MB and cardiac troponin T were used to detect the degree of cardiac damage. The levels of superoxide dismutase, malondialdehyde, glutathione and catalase in serum were measured to observed oxidative stress state. The mRNA levels of cyclophilin D, voltage-dependent anion-selective channel 1 and adenine nucleotide transporter 1 were detected by reverse transcription-quantitative PCR. Western blotting was used to detect the expression of cytochrome c in mitochondria and cytoplasm and cleaved-caspase-9 and pro/cleaved-caspase-3 in cytoplasm in cardiac tissue and primary cardiomyocytes to verify the related signaling pathways. DOX rats showed a series of cardiac damage. However, these damages were alleviated following WG treatment. Further studies showed that WG antagonized DOX cardiotoxicity through inhibiting the release of cytochrome c. WG protected rat heart from DOX damage. The mechanism may be closely related to inhibiting the release of cytochrome c from mitochondria and reducing cardiomyocyte apoptosis caused by caspase activation.

PMID:3512 6708 | PMC:PMC8796616 | DOI:10.3892/etm.2022.11128

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An original method of simulating the articular cartilage in the context of in vitro biomechanical studies investigating the proximal femur

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Exp Ther Med. 2022 Mar;23(3):202. doi: 10.3892/etm.2022.11125. Epub 2022 Jan 5.

ABSTRACT

Biomechanical testing is a necessity given the development of novel implants used in the osteosynthesis of hip fractures. The purpose of biomechanical testing is to recreate realistic conditions similar to the in vivo conditions. Although biomechanical testing of hip arthroplasty has been standardized since the 1970s, there is no consensus at present on testing methodology for osteosynthesis of hip fractures. Most biomechanical studies examining the fractures of the proximal femur in order to optimize implants opt for loading the bone-implant ensemble directly on the femoral head or using a metallic loading part. This loading technique fails to perform a mechanical stress distribution similar to in vivo conditions, which could alter the outcome. The present study aimed to design loading/unloading cups with mechanical properties that r esemble those of the cartilage at the hip level. Through the impression and scanning of the cast models obtained, a digital 3D model was created in STL format and this was processed in order to obtain the computer numerical control (CNC) trajectories of the printing head. For prototyping using additive manufacturing technology, a thermoplastic polymer with biochemical properties, such as tensile strength, that resemble those of the adult hip and a Stratasys FORTUS 250 mc CNC machine were used. Loading/unloading cups with similar anatomy and biomechanical forces compared with those of the adult hip were created, which allowed the experimental simulation of the conditions during walking.

PMID:35126705 | PMC:PMC8794553 | DOI:10.3892/etm.2022.11125

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Benefits and adverse events of melatonin use in the elderly (Review)

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Exp Ther Med. 2022 Mar;23(3):219. doi: 10.3892/etm.2022.11142. Epub 2022 Jan 14.

ABSTRACT

Melatonin is a hormone secreted by the pineal gland in accordance with the circadian rhythm when the light level decreases. Reduction of melatonin secretion with age may be associated with physiological aging in neurodegenerative diseases by affecting the suprachiasmatic nucleus or of the neuronal pathways of transmission to the pineal gland. A significant decrease in melatonin synthesis has been reported in various disorders and diseases, including cardiovascular diseases, metabolic disorders (particularly diabetes type 2), cancer and endocrine diseases. In addition to the fact, that melatonin is a sleep inducer, it also exerts cytoprotective properties as an antioxidant and free radical scavenger. The therapeutic role of melatonin has been demonstrated in sleep disorders, eye damage and cardiovascular disease. The association between melatonin a nd β-blockers has had a positive impact on sleep disorders in clinical trials. Previous studies have reported the anti-inflammatory effect of melatonin by adjusting levels of pro-inflammatory cytokines, including interleukin (IL)-6, IL-1β and tumor necrosis factor-α. Melatonin treatment has been demonstrated to decrease IL-6 and IL-10 expression levels and efficiently attenuate T-cell proliferation. Currently, there is an inconsistency of scientific data regarding the lowest optimal dose and safety of melatonin for long-term use. The aim of the present review was to summarize the evidence on the role of melatonin in various clinical conditions and highlight the future research in this area.

PMID:35126722 | PMC:PMC8796282 | DOI:10.3892/etm.2022.11142

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Telmisartan inhibits bladder smooth muscle fibrosis in neurogenic bladder rats

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Exp Ther Med. 2022 Mar;23(3):216. doi: 10.3892/etm.2022.11140. Epub 2022 Jan 11.

ABSTRACT

Hypertension is associated with bladder symptoms. The present study investigated whether an angiotensin receptor blocker could improve the symptoms and pathological changes associated with a neurogenic bladder (NB). A Sprague-Dawley rat model of NB was constructed. Rats in the sham and model groups were gavaged with saline, and rats in the treatment group were gavaged with telmisartan. Urodynamic parameters, including maximum cystometric capacity, residual urine volume, bladder wet weight, bladder compliance and detrusor pressure, were detected. Masson and H&E staining were performed to assess bladder fibrosis and histopathological changes. The expression levels of basic fibroblast growth factor (bFGF), TGF-β1, Collagen I, Collagen III, and α-smooth muscle actin (α-SMA) were also measured by reverse transcription-quantitative PCR, western b lotting and immunohistochemistry. The model rats exhibited symptoms and pathological changes associated with NB. Treatment with telmisartan reduced maximum cystometric capacity, residual urine volume, bladder compliance and bladder wet weight, and increased detrusor pressure in model rats. The tissue staining results showed that telmisartan exerted an antifibrotic effect. In addition, telmisartan inhibited the expression of bFGF, TGF-β1, Collagen I, Collagen III and α-SMA in model rats. Therefore, the results of the present study indicated that telmisartan may serve as a potential therapeutic agent for NB.

PMID:35126719 | PMC:PMC8796288 | DOI:10.3892/etm.2022.11140

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Identification of key pathways and genes in vestibular schwannoma using bioinformatics analysis

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Exp Ther Med. 2022 Mar;23(3):217. doi: 10.3892/etm.2022.11141. Epub 2022 Jan 13.

ABSTRACT

The aim of the present study is to identify novel promising marks and targets of diagnosis, therapy and prognosis for patients with vestibular schwannoma at the molecular level. The gene expression profiles of GSE54934, GSE39645 and GSE56597 datasets were obtained respectively from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified by comparing between gene expression profiles of the vestibular schwannoma tissues and normal tissues. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analysis were performed. The function and pathway enrichment analysis were performed for DEGs with DAVID. Reverse transcription-quantitative PCR were conducted to confirm the expression of BCL2, AGT, IL6 and ITGA2 in human Schwann cells and vestibular schwannoma cells. A total of 4,025, 1,1291 and 1,513 DEGs were identified from GSE54934, GSE56597 and GSE39645 datasets, respectively. GO and KEGG analysis showed that the mutual upregulated genes were mainly enriched in cell division, mitotic nuclear division, and transition of mitotic cell cycle, whilst mutual downregulated genes were enriched in chemical synaptic transmission, neurotransmitter transport, and synaptic vesicle membrane. Subsequently, 20 genes, including BCL2, AGT, IL6 and ITGA2 were selected as hub genes with high degrees after PPI network analysis. The significant differential expression of those genes were detected among vestibular schwannoma tissues compared with normal nerve tissues. In conclusion, BCL2, AGT, IL6 and ITGA2 are significantly higher expressed in vestibular schwannoma tissues compared with human Schwann tissues. The DEGs identified in the present study provide novel targets for the diagnosis and treatment of vestibular schwannoma.

PMID:35126720 | PMC:PMC8796280 | DOI:10.3892/etm.2022.11141

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Role of antioxidants and oxidative stress in the evolution of acute pancreatitis (Review)

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Exp Ther Med. 2022 Mar;23(3):197. doi: 10.3892/etm.2022.11120. Epub 2022 Jan 5.

ABSTRACT

Acute pancreatitis (AP) is a severe disease with a high prevalence and 3 to 15% mortality worldwide, which can represent an important challenge for the physician. Oxidative stress and antioxidants are involved in AP progression. The mechanisms responsible for the onset and progression of AP are still poorly understood. Previous studies have highlighted the important contribution of antioxidants and oxidative stress in AP. The existence of a relationship between oxidative stress and antioxidants in AP is unquestionable, although a more accurate understanding of the mechanistic pathways involved is required to create a solid basis for potential prevention or treatment strategies. Further investigation is needed to clarify the role of antioxidant status and the severity of AP and to determine the association between oxidative stress and pancreatic enz yme activities. Antioxidant therapy may represent an interesting option for the management of patients with AP, although additional information about the effectiveness of this potential treatment is required.

PMID:35126700 | PMC:PMC8794551 | DOI:10.3892/etm.2022.11120

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Cytokines and Inflammation in Meniere Disease

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Clin Exp Otorhinolaryngol. 2022 Feb 8. doi: 10.21053/ceo.2021.00920. Online ahead of print.

ABSTRACT

Meniere disease (MD) is a rare set of conditions associated with the accumulation of endolymph in the cochlear duct and the vestibular labyrinth with a decrease of endocochlear potential. It is considered a chronic inflammatory disorder of the inner ear with a multifactorial origin. The clinical syndrome includes several groups of patients with a core phenotype: sensorineural hearing loss, episodes of vertigo, and tinnitus with a non-predictable course. Genetic factors and the innate immune response seem to play a central role in the pathophysiology of the condition. Autoimmune MD should be diagnosed if a patient fulfills the diagnostic criteria for MD and one of the following autoimmune disorders: autoimmune thyroid disease, psoriasis, autoimmune arthritis, ankylosing spondylitis, or systemic lupus erythematosus. We summarize the evide nce to support autoimmune MD as an endophenotype in bilateral MD associated with the allelic variant rs4947296 and nuclear factor-kappa B (NF-κB)-mediated inflammation, the role of cytokines (particularly interleukin-1β and tumor necrosis factor-α) in defining a subset of patients with autoinflammation, and the potential role of cytokines as biomarkers to distinguish between patients with MD and vestibular migraine. Finally, we also introduce a list of potential drugs that could regulate the immune response in MD with potential for repurposing in clinical trials.

PMID:35124944 | DOI:10.21053/ceo.2021.00920

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Oral administration of megestrol acetate can increase fat graft survival in a rat model

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J Plast Reconstr Aesthet Surg. 2022 Jan 16:S1748-6815(22)00018-3. doi: 10.1016/j.bjps.2022.01.004. Online ahead of print.

ABSTRACT

Insufficient and inconsistent survival is a significant shortcoming of fat grafts. Reportedly, megestrol acetate (MA) could induce proliferation, migration, and adipogenic differentiation of adipose-derived stem cells in vitro. Thus, we tested whether MA could promote fat graft survival in a rat model. Twenty-eight Sprague-Dawley rats (8 weeks old, male) were divided into two groups: experimental (MA group, n = 14) and control (n = 14). The inguinal fat pad (1 g) was extracted en bloc and re-implanted under the scalp in both groups. MA (100 mg/kg/day) was administered orally for 14 postoperative days in the experimental group. After 6 weeks, the volume and weight of the grafted fat were measured. Histologic examination with hematoxylin and eosin (HE) and real-time polymerase chain reaction (PCR) for vascula r endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and CCAAT/enhancer-binding protein alpha (C/EBP-α) were performed. Perilipin staining was performed to check the viability of grafted fat. Graft fat volume was greater in the MA group, compared with that in the control (P = 0.023). The MA group also had more viable cells, including more adipocytes, and less fibrosis or vacuoles than the control on HE and perilipin staining. MA upregulated the expression of FGF2 (P<0.001), VEGF (P = 0.008), and C/EBP-α (P = 0.002) at the second postoperative week. MA increased survival of grafted fat in an animal model. Increased vascularization and adipogenesis were related to these results. Further human clinical trials are necessary to evaluate adjunctive oral administration of MA after fat grafting to promote graft survival.

PMID:35125304 | DOI:10.1016/j.bjps.2022.01.004

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Breast and abdominal scarring after DIEP flap breast reconstruction: An exploration of patient-reported scar quality

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J Plast Reconstr Aesthet Surg. 2022 Jan 14:S1748-6815(22)00002-X. doi: 10.1016/j.bjps.2021.12.003. Online ahead of print.

ABSTRACT

PURPOSE: This research aimed to explore factors associated with patient-reported breast and abdominal scar quality after deep inferior epigastric perforator (DIEP) flap breast reconstruction (BR).

MATERIAL AND METHODS: This study was designed as a descriptive cross-sectional survey in which women after DIEP flap BR were invited to complete an online survey on breast and abdominal scarring. The online survey was distributed in the Netherlands in several ways in order to reach a diverse population of women. Outcomes were assessed with the Patient Scale of the Patient and Observer Scar Assessment Scale (POSAS). Additional items were assessed with a numeric rating scale (NRS).

RESULTS: A total of 248 women completed the survey. There was a statistically significant worse POSAS scar appraisal for the abdominal scar compared with the breast scar. The vast majority of women reported high scores on at least one scar characteristic of their breast scar or abdominal scar. Overall, color, stiffness, thickness, and irregularity scored higher than pain and itching. Women were only moderately positive about the size, noticeability, location, and the information provided regarding scarring.

CONCLUSION: It is crucial to address the inevitability of scars in patient education before a DIEP flap BR, with a particular focus on the abdominal scar, as women experience abdominal scars significantly worse than their breast scars. Providing more information on the experience of other women and the expected appearance will contribute to having realistic expectations while allowing them to make well-informed decisions.

PMID:35125306 | DOI:10.1016/j.bjps.2021.12.003

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A comparative analysis of associated injuries in the elderly and youth for facial fractures

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J Plast Reconstr Aesthet Surg. 2022 Jan 16:S1748-6815(22)00016-X. doi: 10.1016/j.bjps.2021.12.006. Online ahead of print.

ABSTRACT

INTRODUCTION: High-velocity and high-impact forces can yield life-threatening injuries that are not only limited to the face but can involve other regions of the body. Associated injuries are more frequent in the elderly impacting management and outcomes. The primary objective was to study the association between associated injuries and age groups by identifying epidemiological trends and differences among the elderly and younger population.

METHODS: A retrospective review was conducted from January 2012 to January 2017 at the Royal Adelaide Hospital, Adelaide. A comparative analysis for elderly and younger controls was assessed for associated injuries, etiology, management, and length of stay.

RESULTS: There were 355 elderly and 1884 younger controls for the study. There were differences betwee n gender, alcohol, socioeconomic status, type of facial fracture, mechanism of injury, and associated injuries (p<0.05). The elderly were 3.6 times more likely to have an associated injury compared to the younger cohort (p<0.05). Total limb injuries were 2.2 times more likely in the elderly compared to the younger cohort, and neurological related injuries were 2.7 times more likely (p<0.05). Neurological injuries were most frequent in fall-related injuries, limb injuries in RTA; and soft-tissue injuries for assault, sport, animal, and work (p<0.001). The elderly had longer hospital stays as compared with younger controls (p<0.05).

CONCLUSIONS: Associated injuries are more frequent in the elderly and impact other bodily systems leading to a longer length of stay. In the assessment and management of facial trauma, anatomical and disciplinary boundaries may cross requiring interdisciplinary care.

PMID:35125309 | DOI:10.1016/j.bjps.2021.12.006

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Multiple spontaneous cerebrospinal fluid leaks: a rare case report and review of literature

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AME Case Rep. 2022 Jan 25;6:5. doi: 10.21037/acr-21-36. eCollection 2022.

ABSTRACT

While a spontaneous cerebrospinal fluid leak (sCSFL) is a rare phenomenon, patients who present with multiple cerebrospinal fluid leaks (mCSFLs) are an even rarer entity. There have been documented cases reported over the last decades, but many with only limited descriptions of each patient. We present a mCSFL patient as a case report and demonstrate the need for future prospective studies to improve further understanding and management of the condition. This is explored through summarizing the literature on mCSFLs to the present time. A 45-year-old obese female presented with a 5-week history of bilateral clear nasal discharge with no previous surgery or trauma. Initially misdiagnosed as allergic rhinitis, nasal discharge was later confirmed positive for beta-2-transferrin and a CT scan revealed multiple bony areas of skull base erosion. The patient underwent image guided endoscopic sinus surgery with multilayer skull base defect repair of three active CSFLs. Three months post-operatively the patient had no evidence of a recurrence. As mCSFL tend to be sporadic and asymptomatic in nature, it is likely they are underreported. Future prospective studies in the area of mCSFLs that take into consideration demographic and geographical information are needed for more accurate interpretation and better recruitment. Additionally, studies need to ensure longer follow-up time due to the underlying chronicity of increased intracranial pressure (ICP) and investigate whether or not a non-active leak site should be repaired or left alone.

PMID:35128313 | PMC:PMC8762381 | DOI:10.21037/acr-21-36

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