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Osteoporosis, a prevalent systemic bone metabolic disorder, primarily affects postmenopausal women and is characterized by increased bone fragility and a heightened risk of fractures. The efficacy of current osteoporosis treatments is often limited by non-specific drug targeting and undesirable off-target skeletal side effects. To address this challenge, we have developed a novel hydroxyapatite-responsive drug delivery system. This system utilizes a self-assembled p-phosphonatocalix[4]arene tetradodecyl ether (PC4A12C), engineered to specifically target and sustain the release of osteoporosis medication at sites of bone remodeling. Our focus centers on icariin (ICA), a drug known for its potent osteogenic properties and minimal adverse effects. In vitro, ICA-loaded PC4A12C (ICA@PC4A12C) demonstrated enhanced proliferation, differentiation, and mineralization in bone marrow mesenchymal stem cells (BMSCs). In vivo, ICA@PC4A12C exhibited superior efficacy in specifically targeting bone tissue, ensuring a controlled and slow release of icariin directly within the bone environment. In an osteoporosis mouse model, treatment with ICA@PC4A12C showed notable enhancement in osteogenic activity and a significant increase in bone density compared to ICA alone. These results demonstrate the potential of PC4A12C as an effective drug carrier in the development of advanced antiosteoporotic drug delivery systems.
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Preparaciones de Acción Retardada , Sistemas de Liberación de Medicamentos , Flavonoides , Células Madre Mesenquimatosas , Osteogénesis , Osteoporosis , Animales , Osteoporosis/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Femenino , Osteogénesis/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Flavonoides/administración & dosificación , Flavonoides/química , Flavonoides/farmacología , Ratones , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Conservadores de la Densidad Ósea/administración & dosificación , Densidad Ósea/efectos de los fármacos , Durapatita/química , Durapatita/administración & dosificación , Ratones Endogámicos C57BL , Liberación de FármacosRESUMEN
OBJECTIVE: To assess the safety and efficacy of antimicrobial peptide PL-5 (Peceleganan) spray in the treatment of wound infections. BACKGROUND: Antimicrobial peptide PL-5 spray is a novel topical antimicrobial agent. METHODS: We conducted a multicenter, open-label, randomized, controlled phase IIb clinical trial to evaluate the efficacy and safety of PL-5 spray, as compared with silver sulfadiazine, in patients with skin wound infections. The primary efficacy outcome was the clinical efficacy rate on the first day after ending the treatment (D8). The secondary efficacy outcome was the clinical efficacy rate on the fifth day posttreatment (D5), the bacteria clearance rate, and the overall efficacy rate at the mentioned 2 time points. The safety outcomes included adverse reactions and pharmacokinetic analysis posttreatment. RESULTS: A total of 220 patients from 27 hospitals in China were randomly assigned to 4 groups. On D8, the efficacy rate was 100.0%, 96.7%, 96.7% for the 1 PL-5, 2 PL-5, 4 PL-5 groups, respectively, as compared with 87.5% for the control group. The efficacy rate among the 4 groups was significantly different ( P <0.05). On D5, the efficacy rate was 100.0%, 93.4%, 98.3% for the 1 PL-5, 2 PL-5, 4 PL-5 groups, respectively, as compared with 82.5% for the control group. The efficacy rate among the 4 groups was significantly different ( P <0.05). The blood concentration of PL-5 was not detectable in pharmacokinetic analysis. No severe adverse event related to the application of PL-5 was reported. CONCLUSIONS: Antimicrobial peptide PL-5 spray is safe and effective for the treatment of skin wound infections. TRIAL REGISTRATION: ChiCTR2000033334.
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Antiinfecciosos Locales , Infección de Heridas , Humanos , Resultado del Tratamiento , Bacterias , China , Método Doble CiegoRESUMEN
BACKGROUND: Circular RNA (circRNA) has been proved to mediate the biological functions of fibroblasts to participate in the regulation of keloid formation. However, the role of circCOL5A1 in keloid formation remains to be further confirmed. METHODS: Primary keloid fibroblasts were isolated form keloid tissues. The expression of circCOL5A1, microRNA (miR)- 877-5p, and early growth response 1 (EGR1) were determined by quantitative real-time PCR. Transfection experiments were carried out to explore the effects of circCOL5A1, miR-877-5p, and EGR1 on cell functions. Cell proliferation, migration, invasion and apoptosis were detected using cell counting kit 8 assay, colony formation assay, transwell assay and flow cytometry. The protein levels of apoptosis markers, extracellular matrix (ECM) markers and EGR1 were measured by western blot analysis. The mechanism of circCOL5A1 was confirmed by RNA pull-down assay, dual-luciferase reporter assay and RIP assay. RESULTS: Our data showed that circCOL5A1 was upregulated in keloid tissues and fibroblasts. Silencing of circCOL5A1 had an inhibition effect on proliferation, migration, invasion and ECM production, while had a promotion effect on apoptosis in keloid fibroblasts. MiR-877-5p could be sponged by circCOL5A1, and its overexpression could repress the biological functions of keloid fibroblasts. The rescue experiments showed that miR-877-5p inhibitor could reverse the suppressive effect of circCOL5A1 knockdown on the biological functions of keloid fibroblasts. In addition, EGR1 was a target of miR-877-5p, and its expression was positively regulated by circCOL5A1. The inhibition effect of miR-877-5p on the biological functions of keloid fibroblasts could be abolished by EGR1 overexpression. CONCLUSION: In summary, circCOL5A1 facilitates keloid fibroblast proliferation, migration, invasion and ECM production through the miR-877-5p/EGR1 axis, thereby potentially promoting keloid formation.
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Quemaduras , Proteína 1 de la Respuesta de Crecimiento Precoz , Queloide , MicroARNs , ARN Circular , Humanos , Movimiento Celular/genética , Proliferación Celular/genética , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Matriz Extracelular , Fibroblastos , Queloide/genética , MicroARNs/genética , ARN Circular/genéticaRESUMEN
OBJECTIVE: To analyze the effect of vacuum sealing drainage (VSD) plus skin grafting on deep burns and the risk factors of postoperative infection. METHODS: A retrospective analysis was conducted on 124 patients with deep burns who were admitted to the Taizhou People's Hospital from February 2019 to February 2021. The 55 patients who underwent traditional dressing change therapy plus second-stage skin grafting became the control group. The remaining 69 patients treated with first stage VSD plus second-stage skin grafting became the observation group. Wound healing time, hospital stay, postoperative infection, wound closure success rate, pain degree, and scar hyperplasia were recorded and compared between the two groups. Logistic regression was used to analyze the risk factors of postoperative infection in patients. RESULTS: Compared with the control group, the observation group had a shorter time of wound healing and hospital stay, lower postoperative wound infection rate and lung infection rate, higher success rate of wound closure, lower pain degree scores on the 7th day after the operation, and less scar hyperplasia (all P<0.05). Logistic regression analysis revealed that burn degree, treatment plan, proportion of burn area, and wound healing time were the factors affecting postoperative infection in patients. CONCLUSION: VSD plus skin grafting have significant effects on deep burns. This combined treatment reduced the occurrence of the wound infection, relieved pain, shortened the healing time and hospitalization time, and reduced the proliferation of scars in the later stage.
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Melanoma is a kind of aggressive skin neoplasms with high mortality. The purpose of this present research was to investigate the effects and potential mechanisms of long-noncoding RNA (lncRNA) MSC antisense RNA 1 (MSC-AS1) in melanoma. MSC-AS1, miR-330-3p and YAP1 expression levels in melanoma tissues and cells were assessed by quantitative real-time polymerase chain reaction. Melanoma cells were evaluated using cell count kit-8, clone formation and ELISA in vitro . The relationship among MSC-AS1, YAP1 and miR-330-3p was validated by pull-down and luciferase reporter assays. Finally, the role of MSC-AS1 in vivo was determined by the xenograft model. Results showed that lncRNA MSC-AS1 was upregulated in melanoma tissues and cells. High expression of MAS-AS1 was positively correlated with a poor prognosis. Pull-down and luciferase reporter demonstrated that miR-330-3p specifically binds directly to YAP1 and MSC-AS1, respectively. MSC-AS1 promoted the expression of YAP1 by downregulating miR-330-3p. Functional experiments suggested that knockdown of MSC-AS1 suppressed the proliferation of melanoma cells and decreased the levels of glutamine, glutamate and α-ketoglutarate, glutaminase and glutamine transporter alanine-serine-cysteine transporter 2. Upregulation of miR-330-3p alleviated the promotion effect of MSC-AS1 overexpression on the proliferation and glutaminolysis of melanoma cells. The above changes could be reversed by YAP1 overexpression. In addition, knockdown of MSC-AS1 dramatically restrained the growth of melanoma cells in xenograft model. In conclusion, our results revealed that MSC-AS1 facilitated the proliferation and glutaminolysis of melanoma cells by regulating miR-330-3p/ YAP1 pathway, suggesting that MSC-AS1 could provide a new idea for the treatment of melanoma.
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Melanoma , MicroARNs , ARN Largo no Codificante , Alanina/genética , Alanina/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Cisteína , Regulación Neoplásica de la Expresión Génica , Glutamatos/genética , Glutamatos/metabolismo , Glutaminasa/genética , Glutaminasa/metabolismo , Glutamina/genética , Glutamina/metabolismo , Humanos , Ácidos Cetoglutáricos , Melanoma/genética , MicroARNs/genética , MicroARNs/metabolismo , Oncogenes , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Serina/metabolismo , Proteínas Señalizadoras YAPRESUMEN
OBJECTIVE: Skin cutaneous melanoma (SKCM) is a common cutaneous malignant tumour. This study explored the expression and the downstream regulation mechanism of guanylate binding protein 2 (GBP2), an interferon (IFN)-induced protein, in SKCM. METHODS: Western blot was employed to verify the expression of SBP2 and its downstream Wnt/ß-catenin pathway-related proteins. We studied the relationship between GBP2 and the SKCM prognosis through database analysis. In vitro, gain-and-loss-of function experiments were conducted in SKCM cells. Cell viability was monitored by the cell counting kit-8 (CCK8) assay, the colony formation assay detected cell proliferation, and apoptosis was verified by flow cytometry. Transwell assay was conducted to test cell invasion and migration, while Western blot was employed to monitor the epithelial-mesenchymal transition (EMT) of SKCM cells. RESULTS: The GBP2 expression in SKCM cells and tissues was lower than normal cells and tissues. GBP2 overexpression inhibited SKCM cell proliferation, migration, invasion, and EMT and promoted cell apoptosis. In contrast, the GBP2 knockdown had the reverse effect. Mechanically, Wnt/ß-catenin was inactivated by GBP2 overexpression and was enhanced by GBP2 knockdown. Drug activation of Wnt/ß-catenin significantly attenuated the malignant phenotypic inhibition induced by GBP2 up-regulation in SKCM cells. CONCLUSION: GBP2 exerts anti-tumour effects by inhibiting the Wnt/ß-catenin pathway in SKCM and is related to a favourable prognosis.
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Proteínas de Unión al GTP/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Melanoma , Neoplasias Cutáneas , Vía de Señalización Wnt/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ensayos de Migración Celular/métodos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Transición Epitelial-Mesenquimal/efectos de los fármacos , Técnicas de Silenciamiento del Gen/métodos , Humanos , Inmunohistoquímica , Melanoma/metabolismo , Melanoma/patología , Células Madre Neoplásicas , Pronóstico , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Melanoma Cutáneo MalignoRESUMEN
This paper reported a new method for the determination of the water distribution in sludge. It was based on a multiple headspace extraction (MHE) procedure to step-wise remove the water vapor from a closed vial containing a sludge sample, followed by a gas chromatographic measurement (GC). By plotting the GC signal of water vapor vs. the headspace extraction number, three different trend lines from the profile can be observed. From which two transition points can be determined and thus the stages for the free water, capillary water, and adsorption water release can be divided. Based on the sum of GC peak areas ate each stage, the content of these water types in the sludge can be calculated through a method calibration. The results showed that the MHE-GC method has a better measurement repeatability (RSD < 18.6%) and sensitivity (limit of quantitation = 0.028%) than the thermal drying method (used as a reference method). There was also a good agreement between the MHE-GC and the reference method on the free water and capillary water analysis. Moreover, the results on the adsorption water and bound water testing by the present method is more justifiable than the reference method.
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Cromatografía de Gases/métodos , Aguas del Alcantarillado/análisis , Agua/análisis , Calibración , Desecación , Presión , Reproducibilidad de los Resultados , Temperatura , Factores de TiempoRESUMEN
PURPOSE: Autologous bone grafting is commonly used in reconstructive hand surgery. Various sources of nonvascularized autologous bone grafts have been described in the literature. However, in some situations, a vascularized bone graft may be needed. Popular vascularized bone grafts are taken from the distal radius, iliac crest, and medial femoral condyle. The purpose of this study was to examine the feasibility of harvesting a free vascularized bone flap from the proximal ulna. METHODS: Latex was injected via the brachial artery to facilitate visualization of perforators in 10 cadaveric specimens. Dissections were performed of the olecranon; all periosteal perforators were noted, and their lengths and diameters recorded. Corticocancellous bone flaps with their supplying pedicles were harvested. Three additional fresh specimens were injected with india ink via the pedicles to demonstrate perfusion of the harvested bone flap. RESULTS: Consistent vascular anatomy supplied the olecranon. A perforator from the posterior ulnar recurrent artery supplied the proximal ulna and olecranon, from which a vascularized bone flap can be harvested. Branches to the flexor carpi ulnaris muscle may allow chimeric flaps to be harvested. Average pedicle length was 5.8 cm and average pedicle diameter was 2.4 mm. India ink injection of the pedicles showed perfusion of the periosteum as well as intraosseous cancellous bone. CONCLUSIONS: A vascularized olecranon free flap can be harvested based on the posterior ulnar recurrent artery. Vascular anatomy is consistent and flap harvest is simple and straightforward in all cadaveric specimens. CLINICAL RELEVANCE: A vascularized olecranon free flap represents a potential new surgical option when vascular bone flap reconstruction is considered.
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Trasplante Óseo , Olécranon , Cadáver , Antebrazo , Humanos , Olécranon/cirugía , Cúbito/cirugíaRESUMEN
BACKGROUND: Proximally based, pedicled flexor carpi ulnaris (FCU) muscle flap has been described previously for soft tissue coverage of the proximal forearm and elbow. No studies have been done on the distal muscular perforators and its use as a distally based flap. METHODS: Ten fresh-frozen cadaveric dissections were done. Specimens were injected with latex to facilitate identification of the perforators. Distal muscular perforators were dissected and distances of the pedicles from the distal wrist crease and ulnar styloid were measured and recorded. A clinical case is also presented where a distally based FCU muscle flap was used for coverage in a patient with median nerve neuroma. RESULTS: A distal muscular perforator and a second more proximal perforator were identified in all specimens. The average distance from the most distal muscular perforator to the ulnar styloid was 3.0 cm. The average distance to the wrist crease was 4.6 cm. The more proximal perforators had an average distance to the ulnar styloid and wrist crease of 7.3 cm and 8.8 cm, respectively. At 7 months post-op, the patient who underwent median nerve neurolysis and coverage with pedicled FCU flap had much improved sensation, with complete resolution of pain and tingling, and without any functional deficits. CONCLUSIONS: The use of a distally based FCU muscle flap is a good option for soft tissue coverage of the distal forearm, wrist, and hand. The distal muscular perforators from the ulnar artery exhibit a relatively consistent anatomy.
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Arteria Braquial/anatomía & histología , Músculo Esquelético/irrigación sanguínea , Colgajos Quirúrgicos/irrigación sanguínea , Cadáver , Humanos , Masculino , Nervio Mediano/cirugía , Neuropatía Mediana/etiología , Neuropatía Mediana/cirugía , Persona de Mediana Edad , Neuroma/cirugía , Neoplasias del Sistema Nervioso Periférico/cirugíaRESUMEN
AIM To investigate the effects of asiatic acid (AA) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD)-like motor symptoms in mice and its neuroprotective mechanism.METHODS Forty-five male C57BL/6 mice,except the nine mice in control group,were induced to be the PD models by peritoneal injection of 25 mg/kg MPTP for seven days and then were randomly assigned to model group,low-dose,high-dose AA groups and positive control group.Both the control group and the model group were administered with 0.5% sodium carboxyl methyl cellulose (CMC-Na) solution,the AA groups were dosed with 12.5 mg/kg and 25 mg/kg AA,respectively,and the positive control group was given 75 mg/kg daily intragastric gavage of levodopa for eleven days.On the twelfth day,behavioral tests were performed.Tyrosine hydroxylase (TH) positive cells in substantia nigra were detected by immunohistochemistry.The mRNA expressions of iNOS,COX-2,TNF-α,IL-1β,and malonaldehyde (MDA) content in midbrain were measured.The levels of IL-1 β and TNF-α in the serum were detected using ELISA kits.RESULTS The mice treated with asiatic acid performed better in behavior tests than those in the model group (P <0.05,P <0.01).In addition,asiatic acid effectively protected the dopaminergic neurons in the substantia nigra due to upregulated TH expression and increased number of TH positive cells (P < 0.05).The asiatic acid-treated mice had their mRNA expressions of IL-1β,TNF-α,iNOS and COX-2 in midbrain markedly suppressed (P <0.05,P <0.01),and a significant MDA level decrease in the midbrain tissue as well (P < 0.01).Furthermore,reductions of IL-1 β and TNF-α contents in the serum were observed (P < 0.05,P < 0.01).CONCLUSION Asiatic acid attenuates motor dysfunction and dopaminergic neuronal deficits in PD mice,and the neuroprotective mechanisms may attribute to its anti-oxidative and anti-inflammatory activities.
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Although several donor nerves can be chosen to repair avulsed brachial plexus nerve injury, available nerves are still limited. The purpose of this study is to validate whether the vagus nerve (VN) can be used as a donor. Eighteen Sprague-Dawley male rats were divided into three groups (n = 6). The right musculocutaneous nerve (McN) was transected with differing subsequent repair. (1) HS-VN group: a saphenous nerve (SN) graft-end was helicoidally wrapped round the VN side (epi-and perineurium was opened) with a 30 ° angle, distal SN end was coapted to the McN with end-to-end repair. (2) EE-PN group: a SN was interpositionally grafted between the transected phrenic nerve (PN) and the McN by end-to-end coaptation. (3) Sham control group: McN was transected and not repaired and postoperative vital signs were checked daily. At three months, electrophysiology, tetanic force, wet biceps muscle weight, and histology were evaluated. Every tested mean value in HS-VN group was significantly greater than the EE-PN or the sham control groups (p < 0.05 or p < 0.005). The mean recovery ratio of regenerated nerve fibers was 96% and, in HS-VN group, the mean recovery ratio of CMAP was 79%. No vital signs changed in any group. There was no statistical difference (p > 0.5) between the mean VN nerve-fiber numbers of the segments proximal (2237 ± 134) and distal (2150 ± 156) to the VN graft-attachment site. Histological analysis revealed no axon injury or intraneural scarring at any point along the VN. This study demonstrated that VN is a practical and reliable donor nerve for end-to-side nerve transfer. © 2017 Wiley Periodicals, Inc.
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Nervio Musculocutáneo/cirugía , Transferencia de Nervios/métodos , Nervio Vago/trasplante , Animales , Regeneración Nerviosa/fisiología , Ratas , Ratas Sprague-DawleyRESUMEN
Background After peripheral nerve injury, there is an increase in calcium concentration in the injured nerves. Our previous publications have shown that increase in calcium concentration correlated well with degree of nerve injury and that local infusion of calcitonin has a beneficial effect on nerve recovery. Schwann cells play a pivotal role in regeneration and recovery. We aim to examine cultured Schwann cell survivals in various concentrations of calcium-containing growth media and the effect of calcitonin in such media. Methods To establish baseline in postinjury state, crush injury was induced in male Sprague-Dawley rats' sciatic nerves. Extra- and intraneural calcium concentrations were measured. To study Schwann cell survival, uninjured sciatic nerve segment was harvested and cultured in media containing various amounts of calcium. To study the effect of calcitonin, nerve harvest and culture were done in four additional media: (1) normal control, (2) normal control with calcitonin, (3) high calcium medium, and (4) high calcium medium with calcitonin. Schwann cells were studied and analyzed under fluorescent conditions. Results With increasing calcium concentration, there was a significant decrease in the number of Schwann cells. For the experimental groups, in which calcitonin had been added to the growth medium, there were similar amounts of Schwann cells present in both high and low calcium-containing medium. Conclusion Schwann cells are sensitive to increasing calcium concentration. Calcitonin counteracts the detrimental effects of high calcium on Schwann cell survival. This can have significant future clinical implications for patients with peripheral nerve injuries.
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Calcio/metabolismo , Regeneración Nerviosa/efectos de los fármacos , Células de Schwann/citología , Células de Schwann/efectos de los fármacos , Nervio Ciático/lesiones , Nervio Ciático/metabolismo , Animales , Conservadores de la Densidad Ósea/farmacología , Calcitonina/farmacología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Masculino , Compresión Nerviosa , Regeneración Nerviosa/fisiología , Ratas , Ratas Sprague-Dawley , Recuperación de la Función , Nervio Ciático/efectos de los fármacos , Nervio Ciático/fisiopatologíaRESUMEN
Peripheral nerve injury can have a devastating effect on daily life. Calcium concentrations in nerve fibers drastically increase after nerve injury, and this activates downstream processes leading to neuron death. Our previous studies showed that calcium-modulating agents decrease calcium accumulation, which aids in regeneration of injured peripheral nerves; however, the optimal therapeutic window for this application has not yet been identified. In this study, we show that calcium clearance after nerve injury is positively correlated with functional recovery in rats suffering from a crushed sciatic nerve injury. After the nerve injury, calcium accumulation increased. Peak volume is from 2 to 8 weeks post injury; calcium accumulation then gradually decreased over the following 24-week period. The compound muscle action potential (CMAP) measurement from the extensor digitorum longus muscle recovered to nearly normal levels in 24 weeks. Simultaneously, real-time polymerase chain reaction results showed that upregulation of calcium-ATPase (a membrane protein that transports calcium out of nerve fibers) mRNA peaked at 12 weeks. These results suggest that without intervention, the peak in calcium-ATPase mRNA expression in the injured nerve occurs after the peak in calcium accumulation, and CMAP recovery continues beyond 24 weeks. Immediately using calcium-modulating agents after crushed nerve injury improved functional recovery. These studies suggest that a crucial time frame in which to initiate effective clinical approaches to accelerate calcium clearance and nerve regeneration would be prior to 2 weeks post injury. © 2017 Wiley Periodicals, Inc.
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Calcitonina/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Calcio/metabolismo , Nifedipino/farmacología , Traumatismos de los Nervios Periféricos/metabolismo , Recuperación de la Función/fisiología , Animales , Masculino , Compresión Nerviosa , Regeneración Nerviosa/efectos de los fármacos , Regeneración Nerviosa/fisiología , Ratas , Ratas Sprague-DawleyRESUMEN
INTRODUCTION: After nerve injury, calcium concentrations in intranerve fibers quickly increase. We have shown that functional recovery of injured nerves correlates with calcium absorption. A slight increase in calcium reduces the number of Schwann cells present. Calcitonin therapy greatly improves regeneration by accelerating calcium absorption. We examined the effect of adding calcitonin to higher concentration calcium media on cultured Schwann cells. METHODS: The cells, isolated from intact sciatic nerves, were cultured with normal or higher concentration calcium media with or without calcitonin. Schwann cells were incubated with anti-S-100, goat-anti-mouse, and propidium iodide and then viewed through fluorescent light and phase-contrast microscopy for observation and analysis. RESULTS: The cells in each calcitonin-containing medium showed many Schwann cells, however, the cells in the higher concentration calcium media showed fewer and more defective Schwann cells. CONCLUSION: These results show that calcitonin protects against the harmful effects of excessive calcium encountered in peripheral nerve injury. Muscle Nerve 56: 768-772, 2017.
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Calcitonina/farmacología , Calcio/metabolismo , Células de Schwann/efectos de los fármacos , Células de Schwann/metabolismo , Animales , Conservadores de la Densidad Ósea/farmacología , Calcio/farmacología , Células Cultivadas , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Asiatic acid (AA), a pentacyclic triterpene found in, displays significant anti-proliferative effects on cancer cellsalthough the underlying mechanism of this effect remains unknown. This study investigated the efficacy and mechanism of action of AA against lung cancer bothand. Using the MTT assay, AA was found to induce apoptosis in a dose- and time-dependent manner, an effect enhanced by pretreatment with an autophagy inhibitor. It also elevated expression of microtubule-associated protein 1 light chain 3 (LC3) and decreased the expression of p62. Furthermore, exposure to AA resulted in collapse of the mitochondrial membrane potential and generation of reactive oxygen species (ROS), suggesting mitochondria are the target of AA. In the mouse lung cancer xenograft model, oral administration of AA significantly inhibited tumor volume and weight accompanied by significant apoptosis of lung cancer cells. In addition, it led to a significant decrease in the expression of proliferating cell nuclear antigen (PCNA). In summary, the results show that AA significantly reduces lung cancer cell growth bothandand that the associated apoptosis is mediated through mitochondrial damage.
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BACKGROUND: Insidious cumulative brain injury from motor vehicle-induced whole-body vibration (MV-WBV) has not yet been studied. The objective of the present study is to validate whether whole-body vibration for long periods causes cumulative brain injury and impairment of the cerebral function. We also explored a preventive method for MV-WBV injury. METHODS: A study simulating whole-body vibration was conducted in 72 male Sprague-Dawley rats divided into 9 groups (N = 8): (1) 2-week normal control; (2) 2-week sham control (in the tube without vibration); (3) 2-week vibration (exposed to whole-body vibration at 30 Hz and .5 G acceleration for 4 hours/day, 5 days/week for 2 weeks; vibration parameters in the present study are similar to the most common driving conditions); (4) 4-week sham control; (5) 4-week vibration; (6) 4-week vibration with human apolipoprotein A-I molecule mimetic (4F)-preconditioning; (7) 8-week sham control; (8) 8-week vibration; and (9) 8-week 4F-preconditioning group. All the rats were evaluated by behavioral, physiological, and histological studies of the brain. RESULTS: Brain injury from vibration is a cumulative process starting with cerebral vasoconstriction, squeezing of the endothelial cells, increased free radicals, decreased nitric oxide, insufficient blood supply to the brain, and repeated reperfusion injury to brain neurons. In the 8-week vibration group, which indicated chronic brain edema, shrunken neuron numbers increased and whole neurons atrophied, which strongly correlated with neural functional impairment. There was no prominent brain neuronal injury in the 4F groups. CONCLUSIONS: The present study demonstrated cumulative brain injury from MV-WBV and validated the preventive effects of 4F preconditioning.
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Lesiones Encefálicas/tratamiento farmacológico , Péptidos/uso terapéutico , Vibración , Accidentes de Tránsito , Animales , Lesiones Encefálicas/prevención & control , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Histological analysis remains a cornerstone approach for the investigation of peripheral nerve regeneration. This study investigates a newly recognized histological difference between peripheral and central zones within the regenerating nerve trunks. PURPOSE: The purpose of the study was to determine if the nerve axonal area (NXA) in regenerating peripheral nerves differs within central and peripheral areas, when viewed in cross-section. METHODS: A total of 14 rats were divided into two groups, and subjected to different injuries to the right sciatic nerve. Group 1: Transection injury with immediate repair. Group 2: Crush injury without any treatment. The left sciatic nerve was left uninjured and served as a control in each rat. Following 4 weeks of recovery, nerve trunk cross-sections were prepared. Computerized techniques were then employed to divide nerve sections into central and peripheral zones and calculate corresponding NXA values for subsequent statistical analysis. RESULTS: NXA of injured nerves was greater within peripheral as compared with the central zones, independent of injury type (p < 0.05). No statistically significant difference existed within the control groups or between the injury methods with regards to NXA regeneration extent. CONCLUSION: NXA in regenerating peripheral nerves was greater in the peripheral zones than within the central zones.
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Axones/patología , Regeneración Nerviosa/fisiología , Traumatismos de los Nervios Periféricos/patología , Traumatismos de los Nervios Periféricos/cirugía , Nervio Ciático/patología , Animales , Biopsia con Aguja , Modelos Animales de Enfermedad , Inmunohistoquímica , Masculino , Procedimientos Neuroquirúrgicos/métodos , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Procedimientos de Cirugía Plástica/métodos , Medición de Riesgo , Nervio Ciático/lesiones , Nervio Ciático/cirugía , Resultado del TratamientoRESUMEN
Insidious brain microinjury from motor vehicle-induced whole-body vibration (WBV) has not yet been investigated. For a long time we have believed that WBV would cause cumulative brain microinjury and impair cerebral function, which suggests an important risk factor for motor vehicle accidents and secondary cerebral vascular diseases. Fifty-six Sprague-Dawley rats were divided into seven groups (n = 8): 1) 2-week normal control group, 2) 2-week sham control group (restrained in the tube without vibration), 3) 2-week vibration group (exposed to whole-body vibration at 30 Hz and 0.5g acceleration for 4 hr/day, 5 days/week, for 2 weeks), 4) 4-week sham control group, 5) 4-week vibration group, 6) 8-week sham control group, and 7) 8-week vibration group. At the end point, all rats were evaluated in behavior, physiological, and brain histopathological studies. The cerebral injury from WBV is a cumulative process starting with vasospasm squeezing of the endothelial cells, followed by constriction of the cerebral arteries. After the 4-week vibration, brain neuron apoptosis started. After the 8-week vibration, vacuoles increased further in the brain arteries. Brain capillary walls thickened, mean neuron size was obviously reduced, neuron necrosis became prominent, and wide-ranging chronic cerebral edema was seen. These pathological findings are strongly correlated with neural functional impairments.
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Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/patología , Vibración/efectos adversos , Análisis de Varianza , Animales , Corteza Cerebral/patología , Modelos Animales de Enfermedad , Suspensión Trasera , Masculino , Aprendizaje por Laberinto/fisiología , Microscopía Electrónica de Transmisión , Arteria Cerebral Media/patología , Arteria Cerebral Media/ultraestructura , Fuerza Muscular/fisiología , Conducción Nerviosa/fisiología , Neuronas/patología , Óxido Nítrico/metabolismo , Oxígeno/metabolismo , Dimensión del Dolor , Ratas , Ratas Sprague-DawleyRESUMEN
INTRODUCTION: After nerve injury, excessive calcium impedes nerve regeneration. We previously showed that calcitonin improved nerve regeneration in crush injury. We aimed to validate the direct effect of calcitonin on transected and repaired nerve. METHODS: Two rat groups (n = 8) underwent sciatic nerve transection followed by direct repair. In the calcitonin group, a calcitonin-filled mini-osmotic pump was implanted subcutaneously, with a catheter parallel to the repaired nerve. The control group underwent repair only, without a pump. Evaluation and comparison between the groups included: (1) compound muscle action potential recording of the extensor digitorum longus (EDL) muscle; (2) tetanic muscle force test of EDL; (3) nerve calcium concentration; and (4) nerve fiber count and calcified spot count. RESULTS: The calcitonin pump group showed superior recovery. CONCLUSIONS: Calcitonin affects injured and repaired peripheral nerve directly. The calcitonin-filled mini-osmotic pump improved nerve functional recovery by accelerating calcium absorption from the repaired nerve. This finding has potential clinical applications.
Asunto(s)
Calcitonina/administración & dosificación , Bombas de Infusión Implantables , Regeneración Nerviosa/efectos de los fármacos , Neuropatía Ciática/tratamiento farmacológico , Potenciales de Acción/efectos de los fármacos , Animales , Calcio/metabolismo , Modelos Animales de Enfermedad , Electromiografía , Colorantes Fluorescentes , Fuerza Muscular/efectos de los fármacos , Músculo Esquelético/fisiopatología , Fibras Nerviosas/patología , Ratas , Ratas Sprague-Dawley , Neuropatía Ciática/patología , Factores de Tiempo , Cicatrización de Heridas/efectos de los fármacosRESUMEN
ObjectiveTo systematically review the efficacy and safety of fast-track surgery (FTS) in perioperative nursing for biliary calculi surgery. MethodsOnline databases of PubMed, Cochrane Library, CBM, CNKI, VIP, and Wanfang Data were comprehensively searched for relevant randomized controlled trials (RCTs). Potential bias was evaluated by Cochrane tools and data were analyzed by RevMan 5.3. ResultsA total of 11 RCTs with 1455 patients were included (738 cases in FTS group and 717 cases in control group). The results of meta-analysis showed that FTS significantly reduced the length of postoperative hospital stay (MD=-4.10, 95% CI: -5.68 to -2.52, P<0.000 01) and hospital costs (MD=-0.47, 95%CI: -0.60 to -0.34, P<0.000 01); meanwhile, FTS shortened the time to gastrointestinal recovery (SMD=-2.05, 95%CI: -2.84 to -1.27, P<0.000 01), as well as the time to first defecation (SMD=-1.27, 95% CI: -2.08 to -0.46, P<0.000 01). As for safety, FTS significantly reduced the total complications of choledocholithiasis (RR=0.53, 95%CI: 0.43-0.65, P<0.000 01) and hepatolithiasis (RR=0.52, 95% CI: 0.35-0.77, P=0.001). ConclusionFTS is effective and safe in perioperative nursing for biliary calculi surgery. It can significantly reduce the length of postoperative hospital stay, enhance gastrointestinal recovery, shorten the time to first defecation, and reduce total complications.