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The Journal of Clinical Investigation Jun 2024Aortic aneurysm is a life-threatening disease with limited interventions, closely related to vascular smooth muscle cells (VSMCs) phenotypic switching. SLC44A2, a member...
Aortic aneurysm is a life-threatening disease with limited interventions, closely related to vascular smooth muscle cells (VSMCs) phenotypic switching. SLC44A2, a member of solute carrier series 44 (SLC44) family, remains under-characterized in the context of cardiovascular diseases. Venn diagram analysis based on microarray and single-cell RNA sequencing identified SLC44A2 as a major regulator of VSMCs phenotypic switching in aortic aneurysm. Screening for Slc44a2 amongst aortic cell lineages demonstrated its predominant location in VSMCs. Elevated levels of SLC44A2 were evidenced in the aorta of both abdominal aortic aneurysm patients and angiotensin II (Ang II)-infused Apoe-/- mice. In vitro, SLC44A2 silencing promoted VSMCs towards a synthetic phenotype, while SLC44A2 overexpression attenuated VSMCs phenotypic switching. VSMCs-specific SLC44A2 knockout mice were more susceptible to aortic aneurysm under Ang II infusion, while SLC44A2 overexpression showed protective effects. Mechanistically, SLC44A2 interaction with NRP1 and ITGB3 activates TGF-β/SMAD signaling, thereby promoting contractile genes expression. Elevated SLC44A2 in aortic aneurysm is associated with upregulated runt-related transcription factor 1 (RUNX1). Furthermore, low dose of lenalidomide (LEN) suppressed aortic aneurysm progression by enhancing SLC44A2 expression. These findings reveal SLC44A2/NRP1/ITGB3 complex is a major regulator of VSMCs phenotypic switching and provide potential therapeutic approach (LEN) for aortic aneurysm treatment.
PubMed: 38916960
DOI: 10.1172/JCI173690 -
Annals of Translational Medicine Jun 2024The abdominal donor site is the most common flap used for breast reconstruction, with flap necrosis a feared complication. The technique of surgical 'delay' involves the... (Review)
Review
BACKGROUND
The abdominal donor site is the most common flap used for breast reconstruction, with flap necrosis a feared complication. The technique of surgical 'delay' involves the inducing of relative ischemia to promote neovascularisation, amongst other metabolic adaptations, and has been used to augment flap vascularity and reduce this complication. There is significant variability in the manner in which flap surgery and surgical delay may be performed, such as the vessels ligated, the presence and degree of flap elevation, and the decision to harvest muscle with the flap, amongst other factors. A formal review of techniques, however, has not yet been performed, and there is no consensus as to the optimal technique for surgical delay.
METHODS
A scoping review of the current literature was undertaken to determine the optimal surgical delay technique in abdominal-based flap surgery. A literature search was conducted across PubMed, Embase, Cochrane, and Medline databases. Data regarding the type of flap surgery, delay techniques, and corresponding clinical outcomes was collected and categorised by technique type.
RESULTS
Nine studies met the inclusion criteria and were included for review. Levels of evidence and rates of complications were compared. The range of surgical delay techniques reported in the literature was described. Surgical delay was found to reduce overall complication rates, and the available data suggests it may be particularly beneficial in high-risk patients.
CONCLUSIONS
The current data support delay as a viable method for reducing rates of complications. Further studies and data are required to compare surgical delay techniques and determine the benefit delay may pose to patients with risk factors.
PubMed: 38911569
DOI: 10.21037/atm-23-306 -
Drug Design, Development and Therapy 2024We aimed to evaluate the effect of intravenous esketamine combined with dexmedetomidine as supplemental analgesia in reducing intraoperative visceral pain... (Randomized Controlled Trial)
Randomized Controlled Trial
Esketamine Combined with Dexmedetomidine to reduce Visceral Pain During elective Cesarean Section Under Combined Spinal-Epidural Anesthesia: A double-Blind Randomized Controlled Study.
PURPOSE
We aimed to evaluate the effect of intravenous esketamine combined with dexmedetomidine as supplemental analgesia in reducing intraoperative visceral pain during elective cesarean section under combined spinal-epidural anesthesia (CSEA).
PATIENTS AND METHODS
A total of 269 parturients scheduled for elective cesarean section under CSEA between May 2023 and August 2023 were assessed. The parturients were randomly allocated to receiving either intravenous infusion of 0.3-mg/kg esketamine combined with 0.5-μg/kg dexmedetomidine (group ED, n=76), 0.5-μg/kg dexmedetomidine (group D, n=76), or normal saline (group C, n=76) after umbilical cord clamping. The primary outcome was intraoperative visceral pain. Secondary outcomes included the visual analog scale (VAS) score for pain evaluation and other intraoperative complications.
RESULTS
The incidence of visceral pain was lower in group ED [9 (12.7%)] than in group D [32 (43.8%)] and group C [36 (48.6%), <0.0001]. The VAS score was also lower in group ED when exploring abdominal cavity [0 (0), <0.0001] and suturing the muscle layer [0 (0), =0.036]. The mean arterial pressure was higher in group D [83 (9) mmHg] and group ED [81 (11) mmHg] than in group C [75 (10) mmHg, <0.0001] after solution infusion. The heart rate after infusion of the solution was lower in group D [80 (12) bpm] than in group C [86 (14) bpm] and group ED [85 (12) bpm, = 0.016]. The incidence of transient neurologic or mental symptoms was higher in group ED compared to group C and group D (76.1% vs 18.9% vs 23.3%, <0.0001).
CONCLUSION
During cesarean section, 0.3-mg/kg esketamine combined with 0.5-μg/kg dexmedetomidine can alleviate visceral traction pain and provide stable hemodynamics. Parturients receiving this regimen may experience transient neurologic or mental symptoms that can spontaneously resolve at the end of the surgery.
Topics: Humans; Dexmedetomidine; Ketamine; Double-Blind Method; Cesarean Section; Female; Adult; Visceral Pain; Anesthesia, Spinal; Pregnancy; Anesthesia, Epidural; Drug Therapy, Combination; Elective Surgical Procedures
PubMed: 38911034
DOI: 10.2147/DDDT.S460924 -
Poultry Science Jun 2024As an anti-myogenic factor, the myostatin (MSTN) gene was mainly considered as a genetic marker to improve meat production. Moreover, an additional effect of the MSTN...
As an anti-myogenic factor, the myostatin (MSTN) gene was mainly considered as a genetic marker to improve meat production. Moreover, an additional effect of the MSTN mutation on reducing fat deposition in various farm animals suggested a potential application of the MSTN gene on regulating fat deposition in poultry species. Although increase in muscle mass resulted from muscle hyperplasia in the MSTN mutant quail, cellular mechanism behind the decrease in fat deposition was not investigated in the quail model. In the current study, to investigate sexual dimorphic association between fat deposition and Mstn mutation in quail, leg and abdominal fat pads from 4-month-old male and female quail were histologically analyzed. Interestingly, abdominal and leg fat pad weights were significantly decreased by the MSTN mutation only in female quail, but not in male quail, showing sexual dimorphism in regulating fat deposition by the MSTN mutation in quail. Histological analysis also revealed that fat cell sizes of leg and abdominal fats were significantly reduced only in female groups aligning with the decreased fat pad weights. Sexual dimorphic effect of the MSTN mutation on fat cell hypotrophy and reduced fat pad weights in quail provided an important scientific finding to be considered on the usage of the MSTN gene as a genetic marker to reduce fat deposition in poultry species.
PubMed: 38909511
DOI: 10.1016/j.psj.2024.103951 -
Biomaterials Jun 2024Biohybrid tissue-engineered vascular grafts (TEVGs) promise long-term durability due to their ability to adapt to hosts' needs. However, the latter calls for sensitive...
Biohybrid tissue-engineered vascular grafts (TEVGs) promise long-term durability due to their ability to adapt to hosts' needs. However, the latter calls for sensitive non-invasive imaging approaches to longitudinally monitor their functionality, integrity, and positioning. Here, we present an imaging approach comprising the labeling of non-degradable and degradable TEVGs' components for their in vitro and in vivo monitoring by hybrid H/F MRI. TEVGs (inner diameter 1.5 mm) consisted of biodegradable poly(lactic-co-glycolic acid) (PLGA) fibers passively incorporating superparamagnetic iron oxide nanoparticles (SPIONs), non-degradable polyvinylidene fluoride scaffolds labeled with highly fluorinated thermoplastic polyurethane (F-TPU) fibers, a smooth muscle cells containing fibrin blend, and endothelial cells. H/F MRI of TEVGs in bioreactors, and after subcutaneous and infrarenal implantation in rats, revealed that PLGA degradation could be faithfully monitored by the decreasing SPIONs signal. The F signal of F-TPU remained constant over weeks. PLGA degradation was compensated by cells' collagen and α-smooth-muscle-actin deposition. Interestingly, only TEVGs implanted on the abdominal aorta contained elastin. XTT and histology proved that our imaging markers did not influence extracellular matrix deposition and host immune reaction. This concept of non-invasive longitudinal assessment of cardiovascular implants using H/F MRI might be applicable to various biohybrid tissue-engineered implants, facilitating their clinical translation.
PubMed: 38906013
DOI: 10.1016/j.biomaterials.2024.122669 -
Frontiers in Cardiovascular Medicine 2024In hypertension (HTN), biomechanical stress may drive matrix remodeling through dysfunctional VSMC activity. Prior evidence has indicated VSMC tension-induced signaling...
INTRODUCTION
In hypertension (HTN), biomechanical stress may drive matrix remodeling through dysfunctional VSMC activity. Prior evidence has indicated VSMC tension-induced signaling through the serum and glucocorticoid inducible kinase-1 (SGK-1) can impact cytokine abundance. Here, we hypothesize that SGK-1 impacts production of additional aortic pathologic markers (APMs) representing VSMC dysfunction in HTN.
METHODS
Aortic VSMC expression of APMs was quantified by QPCR in cyclic biaxial stretch (Stretch) +/- AngiotensinII (AngII). APMs were selected to represent VSMC dedifferentiated transcriptional activity, specifically Interleukin-6 (IL-6), Cathepsin S (CtsS), Cystatin C (CysC), Osteoprotegerin (OPG), and Tenascin C (TNC). To further assess the effect of tension alone, abdominal aortic rings from C57Bl/6 WT mice were held in a myograph at experimentally derived optimal tension (OT) or OT + 30% +/-AngII. Dependence on SGK-1 was assessed by treating with EMD638683 (SGK-1 inhibitor) and APMs were measured by QPCR. Then, WT and smooth muscle cell specific SGK-1 heterozygous knockout (SMC-SGK-1KO) mice had AngII-induced HTN. Systolic blood pressure and mechanical stress parameters were assessed on Day 0 and Day 21. Plasma was analyzed by ELISA to quantify APMs. Statistical analysis was performed by ANOVA.
RESULTS
In cultured aortic VSMCs, expression of all APMs was increased in response to biomechanical stimuli (Stretch +/-AngII,). Integrating the matrix contribution to signal transduction in the aortic rings led to IL-6 and CysC demonstrating SGK-1 dependence in response to elevated tension and interactive effect with concurrent AngII stimulation. CtsS and TNC, on the other hand, primarily responded to AngII, and OPG expression was unaffected in aortic ring experimentation. Both mouse strains had >30% increase in blood pressure with AngII infusion, reduced aortic distensibility and increased PPV, indicating increased aortic stiffness. In WT + AngII mice, IL-6, CtsS, CysC, and TNC plasma levels were significantly elevated, but these APMs were unaffected by HTN in the SMC-SGK-1KO +AngII mice, suggesting SGK-1 plays a major role in VSMC biomechanical signaling to promote dysfunctional production of selected APMs.
CONCLUSION
In HTN, changes in the plasma levels of markers associated with aortic matrix homeostasis can reflect remodeling driven by mechanobiologic signaling in dysfunctional VSMCs, potentially through the activity of SGK-1. Further defining these pathways may identify therapeutic targets to reduce cardiovascular morbidity and mortality.
PubMed: 38903966
DOI: 10.3389/fcvm.2024.1359734 -
International Journal of Medical... 2024Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against...
Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against mouse abdominal aortic aneurysm (AAA) induced by both angiotensin II (AngII) and calcium phosphate (Ca(PO)) , which was characterized with lower incidence of mouse AAA. Moreover, histomorphological staining visually presented more intact elastic fiber and less collagen deposition in abdominal aortas of mice treated by glutamine. Further, we found glutamine inhibited the excessive production of reactive oxide species (ROS), activity of matrix metalloproteinase (MMP), M1 macrophage activation, and apoptosis of vascular smooth muscle cells (VSMCs) in suprarenal abdominal aortas of mice, what's more, the high expressions of MMP-2 protein, MMP-9 protein, pro-apoptotic proteins, and IL-6 as well as TNF-α in protein and mRNA levels in cells treated by AngII were down-regulated by glutamine. Collectively, these results revealed that glutamine protected against mouse AAA through inhibiting apoptosis of VSMCs, M1 macrophage activation, oxidative stress, and extracellular matrix degradation.
Topics: Animals; Aortic Aneurysm, Abdominal; Apoptosis; Mice; Glutamine; Angiotensin II; Macrophage Activation; Muscle, Smooth, Vascular; Humans; Myocytes, Smooth Muscle; Oxidative Stress; Reactive Oxygen Species; Disease Models, Animal; Male; Macrophages; Aorta, Abdominal; Matrix Metalloproteinase 9; Matrix Metalloproteinase 2; Tumor Necrosis Factor-alpha; Interleukin-6; Calcium Phosphates
PubMed: 38903916
DOI: 10.7150/ijms.96395 -
PloS One 2024Pelvic Floor Rehabilitation (PFR) is effective in a selection of patients with low anterior resection syndrome (LARS) after rectal cancer surgery. This study aimed to...
BACKGROUND
Pelvic Floor Rehabilitation (PFR) is effective in a selection of patients with low anterior resection syndrome (LARS) after rectal cancer surgery. This study aimed to identify barriers and enablers to prepare for successful implementation into clinical practice.
METHODS
A qualitative study was performed, guided by the Consolidated Framework for Implementation Research (CFIR). Individual interviews (n = 27) and two focus groups were conducted to synthesize the perspectives of rectal cancer patients, pelvic floor (PF) physiotherapists, and medical experts.
RESULTS
Barriers were found to be the absence of guidelines about LARS treatment, underdeveloped network care, suboptimal patient information, and expectation management upfront to PFR. Financial status is frequently a barrier because insurance companies do not always reimburse PFR. Enablers were the current level of evidence for PFR, the positive relationship between patients and PF physiotherapists, and the level of self-motivation by patients.
CONCLUSION
The factors identified in our study play a crucial role in ensuring a successful implementation of PFR after rectal cancer surgery.
Topics: Humans; Rectal Neoplasms; Female; Qualitative Research; Pelvic Floor; Male; Middle Aged; Aged; Focus Groups; Adult
PubMed: 38900764
DOI: 10.1371/journal.pone.0301518 -
Cureus May 2024Introduction Nonalcoholic fatty liver disease (NAFLD) presents as a multisystem disorder, heightening the risk of developing type 2 diabetes mellitus (T2DM) and...
Introduction Nonalcoholic fatty liver disease (NAFLD) presents as a multisystem disorder, heightening the risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs). Occupation emerges as a significant factor influencing the occurrence of NAFLD. Research indicates that individuals engaged in shift work face an elevated risk of NAFLD, alongside obesity and T2DM, attributed to disruptions in their circadian rhythm, which precipitate hepatic steatosis and inflammation. Remarkably, peripheral neuropathy has been observed in conjunction with advanced liver disorders and NAFLD in the general population. However, the correlation between NAFLD and peripheral neuropathy remains unestablished in shift workers. Objective To identify NAFLD in seemingly healthy rotating shift workers and assess any potential impact of NAFLD on nerve function in this demographic. Methods This cross-sectional study involved 73 apparently healthy nonalcoholic security guards (aged 35 to 60 years) working in rotating shifts. The study included a comprehensive assessment, beginning with a medical history, an evaluation of physical activity, and anthropometric measurements. Confirmation of NAFLD was achieved through abdominal ultrasonography (USG), followed by the analysis of biochemical parameters. Motor and sensory nerve conduction studies (NCS) were conducted on participants with normal vitamin B12 levels using the Aleron electromyograph (EMG) machine (Recorders and Medicare Systems Private Ltd, Budanpur, India). The evaluation encompassed the Median and Common Peroneal motor nerves, as well as Median and Sural sensory nerves. Recorded parameters for motor nerves included distal motor latency (DML), compound muscle action potential (CMAP) amplitude, conduction velocity (CV), and F-wave minimum latency (F-wave), while sensory nerve parameters comprised sensory onset latency (SOL), sensory nerve action potential (SNAP) amplitude, and CV. Results Among 73 healthy security guards working in rotating shifts, 76.1% were diagnosed with NAFLD through abdominal ultrasound. Following participant withdrawals and exclusions due to vitamin B12 deficiency, a comparison of NCS parameters between NAFLD (n=24) and Non-NAFLD (n=12) groups revealed no significant disparities in motor or sensory parameters, except for a slightly diminished CMAP amplitude in the peroneal nerve of NAFLD subjects (8.21±2.83mV vs ±10.22±2.30 mV, p< 0.040). However, these differences fell within normal ranges, indicating no notable impact on peripheral nerve conduction in the presence of NAFLD. Conclusion The results indicate a high prevalence of NAFLD among individuals working rotating shifts. Moreover, the investigation suggests that despite the presence of NAFLD, there is no discernible influence on motor and sensory peripheral nerve conduction, particularly in common peroneal, median, and sural nerves.
PubMed: 38899241
DOI: 10.7759/cureus.60632 -
Frontiers in Oncology 2024To investigate the application value of complete laparoscopy and Da Vinci robot esophagogastric anastomosis double muscle flap plasty in radical resection of proximal...
OBJECTIVE
To investigate the application value of complete laparoscopy and Da Vinci robot esophagogastric anastomosis double muscle flap plasty in radical resection of proximal gastric cancer.
METHOD
A retrospective descriptive study was used. The clinicopathological data of 35 patients undergoing radical operation for proximal gastric cancer admitted to Liaoning Cancer Hospital from January 2020 to December 2023 were collected. Variables evaluated: 1. Transoperative,2. Postoperative, 3. Follow-up. In relation to follow-up, esophageal disease status reflux, anastomosis, nutritional status score, serum hemoglobin, tumor recurrence, and metastasis were investigated. The trans and postoperative variables were obtained from the clinical records and the patients were followed up in outpatient department and by telephone.
RESULT
Among the 35 patients, 17 underwent robotic surgery and 18 underwent laparoscopic surgery. There were 29 males and 6 females. 1) Transoperative: Robotic surgery: The operation time was (305.59 ± 22.07) min, the esophagogastric anastomosis double muscle flap plasty time was (149.76 ± 14.91) min, the average number of lymph nodes cleared was 30, and the average intraoperative blood loss was 30 ml. Laparoscopic surgery: The mean operation time was 305.17 ± 26.92min, the operation time of esophagogastric anastomosis double muscle flap was (194.06 ± 22.52) min, the average number of lymph nodes cleared was 24, and the average intraoperative blood loss was 52.5 ml. 2) Postoperative: Robotic surgery: the average time for patients to have their first postoperative anal emission was 3 days, the average time to first postoperative feeding was 4 days, and the average length of hospitalization after surgery was 8 days. Laparoscopic surgery: the average time for patients to have their first postoperative anal emission was 5 days, the average time to first postoperative feeding was 6 days, the average length of hospitalization after surgery was 10 days. 3) Follow-up: The follow-up time ranged from 1 to 42 months, with a median follow-up time of 24 months.
CONCLUSION
Complete Da Vinci robot and laparoscopic esophagogastric anastomosis double muscle flap plasty for radical resection of proximal gastric cancer can minimize surgical incision, reduce abdominal exposure, accelerate postoperative recovery of patients, and effectively prevent reflux esophagitis and maintain good hemoglobin concentration and nutritional status. The advantages of robotic surgery is less intraoperative bleeding and faster post-surgical recovery, but it is relatively more expensive.
PubMed: 38898957
DOI: 10.3389/fonc.2024.1395549