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Repetitive motion or exercise is associated with oxidative stress and muscle inflammation, which can lead to declining grip strength and muscle damage. Oleanolic acid and ursolic acid have anti-inflammatory and antioxidant properties and can be extracted from Chaenomeles speciosa through ultrasonic sonication. We investigated the association between grip strength declines and muscle damage induced by lambda carrageenan (LC) injection and exercise exposure in rats. We also assessed the reparative effects of transdermal pretreatment and post-treatment with C. speciosa extracts (CSEs) by using a supersonic atomizer. The half-maximal inhibitory concentration (IC50) of CSEs for cells was 10.5 mg/mL. CSEs significantly reduced the generation of reactive oxygen species and inflammatory factors (interleukin [IL]-6 and IL-1ß) in in vitro cell tests. Rats subjected to LC injection and 6 weeks of exercise exhibited significantly increased inflammatory cytokine levels (IL-1ß, TNF-α, and IL-6). Hematoxylin and eosin staining revealed inflammatory cell infiltration and evident muscle damage in the gastrocnemius muscle, which exhibited splitting and the appearance of the endomysium and perimysium. The treated rats' grip strength significantly declined. Following treatment with CSEs, the damaged muscles exhibited decreased IL-1ß, TNF-α, and IL-6 levels and normal morphologies. Moreover, grip strength significantly recovered. Pretreatment with CSEs yielded an immediate and significant increase in grip strength, with an increase of 180% and 165% occurring in the rats exposed to LC injection and exercise within the initial 12 h period, respectively, compared with the control group. Pretreatment with CSEs delivered transdermally using a supersonic atomizer may have applications in sports medicine and training or competitions.
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In this study, a spindle-type nozzle was designed to accelerate poly-L-lactic acid (PLLA) microparticles to supersonic velocities for the transdermal delivery of these microparticles to rats. This approach is needle- and pain-free and enhances skin collagen regeneration. The addition of PLLA microparticles at a concentration of 2 mg/mL did not hinder the growth of 3 T3 fibroblasts and Raw264.7 macrophages. The TNF-α assay revealed no obvious inflammation effect of PLLA microparticles at a concentration of 1 mg/mL. A time-lapse recording revealed that after being cocultured with PLLA microparticles for 24 h, Raw264.7 macrophages gradually approached and surrounded the PLLA microparticles. When 3 T3 fibroblasts were cocultured with Raw264.7 macrophages, which were stimulated using PLLA microparticles, collagen synthesis was increased by approximately 60 % compared with that in samples without PLLA microparticles. In vivo animal experiments indicated that after the transdermal delivery of 10 shots of PLLA microparticles through the supersonic atomizer, no obvious changes or damage to the back skin of Sprague-Dawley rats was observed. More importantly, numerous PLLA microparticles penetrated the rat epidermis into the dermal layer. We found macrophages and fibroblasts present close to the PLLA microparticles. Moreover, only mild or no inflammation reaction was observed. Masson staining revealed that after 6-week implantation, 6 % and 12 % of PLLA microparticles significantly stimulated collagen regeneration in 6-week-old and 32-week-old rats. In addition, picrosirius red staining revealed a significant increase in collagen regeneration, especially for type III collagen, following the 6-week implantation of PLLA microparticles. In summary, this study demonstrated an easy, pain-free, nondestructive approach for introducing PLLA microparticles into the dermal layer by using a supersonic atomizer to stimulate collagen regeneration in vivo.
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Poliésteres , Piel , Ratas , Animales , Ratas Sprague-Dawley , ColágenoRESUMEN
BACKGROUND: Liver-type fatty acid-binding protein (L-FABP) is widely expressed in hepatocytes and plays a role in lipid metabolism. It has been demonstrated to be overexpressed in different types of cancer; however, few studies have investigated the association between L-FABP and breast cancer. The aim of this study was to assess the association between plasma concentrations of L-FABP in breast cancer patients and the expression of L-FABP in breast cancer tissue. METHOD: A total of 196 patients with breast cancer and 57 age-matched control subjects were studied. Plasma L-FABP concentrations were measured using ELISA in both groups. The expression of L-FABP in breast cancer tissue was examined using immunohistochemistry. RESULT: The patients had higher plasma L-FABP levels than the controls (7.6 ng/mL (interquartile range 5.2-12.1) vs. 6.3 ng/mL (interquartile range 5.3-8.5), p = 0.008). Multiple logistic regression analysis showed an independent association between L-FABP and breast cancer, even after adjusting for known biomarkers. Moreover, the rates of pathologic stage T2+T3+T4, clinical stage III, positive HER-2 receptor status, and negative estrogen receptor status were significantly higher in the patients with an L-FABP level greater than the median. Furthermore, the L-FABP level gradually increased with the increasing stage. In addition, L-FABP was detected in the cytoplasm, nuclear, or both cytoplasm and nuclear of all breast cancer tissue examined, not in the normal tissue. CONCLUSIONS: Plasma L-FABP levels were significantly higher in the patients with breast cancer than in the controls. In addition, L-FABP was expressed in breast cancer tissue, which suggests that L-FABP may be involved in the pathogenesis of breast cancer.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Proteínas de Unión a Ácidos Grasos , Biomarcadores , Hígado/metabolismoRESUMEN
Articular cartilage may regenerate poorly after injury or during aging. In vitro, farnesol can modulate extracellular matrix synthesis and restore chondrocyte phenotypes by increasing type II collagen (COL II) and glycosaminoglycan (GAG) production. Here, we evaluated farnesol's preventive and reparative effects against osteoarthritis (OA) in vivo. We induced OA in rabbits through resection of the lateral collateral ligament and meniscus. After 2 weeks, the affected limb was treated with 0.5 ml of 0.4 mM farnesol, hyaluronan (HA) nanoparticle-encapsulated 0.8 mM farnesol (Farn/HA), or HA nanoparticles intra-articularly. After 2 and 6 treatment weeks, synovial inflammatory cytokine levels were analyzed. We also removed the entire joint cartilage from lateral femoral condyles for histological investigation. The half-maximum inhibitory concentration of farnesol was 0.5 mM. Farn/HA had relatively low cytotoxicity showing cells remained viable after being treated with 1 mM a concentration Farn/HA. Untreated lateral condyle exhibited extensive wear. By contrast, 0.4 mM farnesol or 0.8 mM Farn/HA led to a relatively transparent and bright appearance. After 2 and 6 treatment weeks, farnesol, particularly 0.8 mM Farn/HA, reduced matrix metalloproteinase 1 and 13 levels considerably. Therefore, 0.8 mM Farn/HA, which enabled slow drug release, demonstrated the highest anti-inflammatory and OA preventive effects. After 6 treatment weeks, farnesol also promoted COL II and GAG synthesis and, thus, aided healing.
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Skeletal muscle atrophy is a disorder characterized by reductions in muscle size and strength. Cumin extract (CE) possesses anti-inflammatory, antioxidant, and hypoglycemic properties. Its pharmaceutical applications are hindered by its low water solubility and by its cytotoxicity when administered at high doses. In this study, we have developed a simplified water distillation method using a rotary evaporator to isolate the active components in cumin seeds. The anti-inflammatory effects of CE and its potential to ameliorate skeletal muscle atrophy in rats with streptozotocin (STZ)-induced diabetes were evaluated. The half-maximal inhibitory concentration (IC50) of CE for cells was 80 µM. By encapsulating CE in chitosan nanoparticles (CECNs), an encapsulation efficacy of 87.1% was achieved with a slow release of 90% of CE after 24 h of culturing, resulting in CECNs with significantly reduced cytotoxicity (IC50, 1.2 mM). Both CE and CECNs significantly reduced the inflammatory response in interleukin (IL)-6 and IL-1ß assays. STZ-induced diabetic rats exhibited sustained high blood glucose levels (>16.5 mmol/L), small and damaged pancreatic ß islets, and skeletal muscle atrophy. CE and CECN treatments ameliorated skeletal muscle atrophy, recovered muscle fiber striated appearance, increased grip strength, and decreased IL-6 level. Furthermore, CE and CECNs led to a reduction of damage to the pancreas, restoring its morphological phenotype, increasing serum insulin levels, and lowering blood glucose levels in STZ-induced diabetic rats. Taken together, treatment with CECNs over a 6-week period yielded positive ameliorative effects in STZ-induced rats of muscle atrophy.
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Airborne fine particulate matter (PM2.5) is a severe problem and is associated with health issues including liver diseases. Workers performing manual labor tend to be alcohol consumers during work, where they are also exposed to PM2.5. Long-term PM2.5 exposure can increase oxidative stress, leading to inflammation. Whether long-term exposure to air pollution and alcohol synergistically increases liver fibrosis risk warrants investigation. Oleanolic acid (OA)-a triterpenoid-has antioxidant and anti-inflammatory activities, but its low water solubility and cytotoxicity impair its potential applications. In this study, we fabricated liposomal OA nanoparticles (Lipo-OAs); then, we evaluated the anti-inflammatory effect on exposed cells and the ameliorative effect of Lipo-OAs on PM2.5 and alcohol-induced liver fibrosis in mice. The half maximal inhibitory concentration of PM2.5 for hepatic stellate cells was 900 µg/mL; at a concentration of ≥600 µg/mL, PM2.5 significantly increased interleukin-6 and tumor necrosis factor-α production. OA encapsulation in Lipo-OAs, 353 ± 140 nm in diameter with 79% encapsulation efficiency, significantly reduced OA cytotoxicity. Lipo-OAs treatment significantly reduced alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase levels; histologically, it alleviated steatosis and improved Ishak's modified HAI score. In conclusion, Lipo-OAs have potential anti-inflammatory and reparative effects for PM2.5 and alcohol-induced liver injury treatment.
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Cirrhosis refers to irreversible liver damage where healthy tissue is replaced by scar tissue, resulting in impaired liver function. There is no cure and current treatments only prevent further liver damage; thus, novel therapeutic options are urgently needed. Here, we report a new approach that enables the formation of self-assembled 3D spheroids of adipose-derived stem cells (ADSCs) and murine hepatocytes (AML12) via reconstituted collagen fibers. Compared with the spheroids formed in the commercially available EZSHERE dish, the collagen fiber-based ADSC/hepatocyte spheroids offer a notable benefit in structure formation and paracrine factor secretion. To test the regenerative capability of the collagen fiber-based 3D ADSC/hepatocyte spheroids, a rat model of thioacetamide (TAA)-induced liver cirrhosis was employed. The transplantation of the collagen fiber-based 3D ADSC/hepatocyte spheroids show an improvement in liver function and ameliorates pathological liver cirrhosis in TAA-treated rats. In summary, our data show collagen fiber-based self-assembled 3D ADSC/hepatocyte spheroids to possess the excellent regenerative capacity in response to TAA-induced liver injury, promising an alternative therapeutic strategy for liver cirrhosis.
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Hepatocitos/trasplante , Cirrosis Hepática/terapia , Esferoides Celulares/trasplante , Animales , Colágeno/metabolismo , Modelos Animales de Enfermedad , Humanos , Cirrosis Hepática/inducido químicamente , Masculino , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Ratas Sprague-Dawley , TioacetamidaRESUMEN
Osteoarthritis (OA) is a joint disorder characterized by the progressive degeneration of articular cartilage. The phenotype and metabolism behavior of chondrocytes plays crucial roles in maintaining articular cartilage function. Chondrocytes dedifferentiate and lose their cartilage phenotype after successive subcultures or inflammation and synthesize collagen I and X (COL I and COL X). Farnesol, a sesquiterpene compound, has an anti-inflammatory effect and promotes collagen synthesis. However, its potent restoration effects on differentiated chondrocytes have seldom been evaluated. The presented study investigated farnesol's effect on phenotype restoration by examining collagen and glycosaminoglycan (GAG) synthesis from dedifferentiated chondrocytes. The results indicated that chondrocytes gradually dedifferentiated through cellular morphology change, reduced expressions of COL II and SOX9, increased the expression of COL X and diminished GAG synthesis during four passages of subcultures. Pure farnesol and hyaluronan-encapsulated farnesol nanoparticles promote COL II synthesis. GAG synthesis significantly increased 2.5-fold after a farnesol treatment of dedifferentiated chondrocytes, indicating the restoration of chondrocyte functions. In addition, farnesol drastically increased the synthesis of COL II (2.5-fold) and GAG (15-fold) on interleukin-1ß-induced dedifferentiated chondrocytes. A significant reduction of COL I, COL X and proinflammatory cytokine prostaglandin E2 was observed. In summary, farnesol may serve as a therapeutic agent in OA treatment.
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BACKGROUND: The WALANT (wide-awake local anesthesia with no tourniquet) technique was based on local infiltration of lidocaine and epinephrine. This technique has rapidly gained popularity in recent years and can perform most hand operations. This study aimed to investigate the time spent on anesthesia and operation and perform an economic analysis among general anesthesia, wrist block with a tourniquet, and the WALANT technique for the internal fixation of metacarpal fractures. METHODS: We retrospectively reviewed all the single metacarpal fractures managed with the same procedure, open reduction, and internal fixation with the plate between January 2015 and December 2019. They were divided into three groups according to the method of anesthesia: (1) general anesthesia (GA group), (2) wrist block with a tourniquet (WB group), and (3) WALANT technique (WALANT group). We collected and analyzed patient demographic data, perioperative or postoperative complications, number of hospital days, and postoperative functional recovery assessment. RESULTS: A total of 63 patients met the inclusion criteria, including 24 in the GA group, 28 in the wrist block group using a tourniquet, and 11 in the WALANT group. There were no complications during the operation and follow-up in each group. The GA group had an average of 32.8 min of anesthesia time, significantly longer than the other two groups. However, there is no significant difference regarding surgical time among the presenting three groups. The discomfort of vomiting and nausea after surgery occurred in 20 patients in the GA group (38.1%). Nevertheless, there was no postoperative vomiting and nausea present in both the WB and WALANT groups. Most patients achieved full recovery of pre-injury interphalangeal and metacarpophalangeal motion at the final assessment of functional recovery. CONCLUSIONS: The patients undergoing metacarpal fixation surgery under WALANT or WB had significantly less anesthesia time and postoperative vomiting and nausea. Moreover, there was no difference in surgical time and intraoperative complications. The time-related reduction improved the utilization of the operation room for additional cases. The reduction of the preoperative examination, anesthesia fee, postoperative recovery room observation, and hospitalization can effectively reduce medical costs. Furthermore, the WALANT group is more acceptable because of no tourniquet, which commonly causes discomfort.
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Huesos del Metacarpo , Anestesia General , Análisis Costo-Beneficio , Humanos , Huesos del Metacarpo/cirugía , Dolor Postoperatorio/prevención & control , Estudios Retrospectivos , MuñecaRESUMEN
Negative pressure wound therapy (NPWT) is usually applied in wound management and soft-tissue salvage after the development of complications. However, immediate postoperative application of NPWT over the flap coverage is seldom reported. We evaluate the effectiveness of immediate postoperative application of NPWT following fasciocutaneous or muscle flap coverage for lower leg reconstruction. A retrospective review of patients who underwent either fasciocutaneous or muscle flap coverage of lower leg soft-tissue defects applied with NPWT immediately after surgery was conducted in a level I trauma center. Sixteen patients, with an average age of 51.2 years, were included in the study. Nine patients had trauma-related soft-tissue loss, six had subsequent soft-tissue defects after debridement, and one had burn injury. Two patients had been treated with free anterolateral thigh flaps, 11 with pedicle flaps, and three with muscle flaps. All flaps survived except for those in two patients with venous congestion on postoperative day 1, which needed further debridement and skin grafting. Therefore, the use of immediate incisional NPWT is an alternative for wound care following flap coverage. The U-shaped design allows easy flap observation and temperature check. Furthermore, this method eliminates any concerns of vascular pedicle compression under negative pressure.
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Pierna/cirugía , Terapia de Presión Negativa para Heridas/métodos , Procedimientos de Cirugía Plástica/métodos , Colgajos Quirúrgicos/cirugía , Adulto , Anciano , Femenino , Humanos , Hiperemia/epidemiología , Hiperemia/etiología , Masculino , Persona de Mediana Edad , Músculo Esquelético/cirugía , Terapia de Presión Negativa para Heridas/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Procedimientos de Cirugía Plástica/efectos adversosRESUMEN
Acne vulgaris is a highly prevalent skin disorder requiring treatment and management by dermatologists. Antibiotics such as clindamycin are commonly used to treat acne vulgaris. However, from both medical and public health perspectives, the development of alternative remedies has become essential due to the increase in antibiotic resistance. Topical therapy is useful as a single or combined treatment for mild and moderate acne and is often employed as maintenance therapy. Thus, the current study investigated the anti-inflammatory, antibacterial, and restorative effects of sesquiterpene farnesol on acne vulgaris induced by Cutibacterium acnes (C. acnes) in vitro and in a rat model. The minimum inhibitory concentration (MIC) of farnesol against C. acnes was 0.14 mM, and the IC50 of 24 h exposure to farnesol in HaCaT keratinocytes was approximately 1.4 mM. Moreover, 0.8 mM farnesol exhibited the strongest effects in terms of the alleviation of inflammatory responses and abscesses and necrotic tissue repair in C.acnes-induced acne lesions; 0.4 mM farnesol and clindamycin gel also exerted similar actions after a two-time treatment. By contrast, nearly doubling the tissue repair scores, 0.4 mM farnesol displayed great anti-inflammatory and the strongest reparative actions after a four-time treatment, followed by 0.8 mM farnesol and a commercial gel. Approximately 2-10-fold decreases in interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α, found by Western blot analysis, were predominantly consistent with the histopathological findings and tissue repair scores. The basal hydroxypropyl methylcellulose (HPMC) gel did not exert anti-inflammatory or reparative effects on rat acne lesions. Our results suggest that the topical application of a gel containing farnesol is a promising alternative remedy for acne vulgaris.
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Antibacterianos/química , Farnesol/química , Propionibacterium acnes/metabolismo , Sesquiterpenos/química , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/metabolismo , Administración Cutánea , Animales , Antibacterianos/farmacología , Farnesol/farmacología , Células HaCaT , Humanos , Derivados de la Hipromelosa/metabolismo , Interleucinas/metabolismo , Masculino , Pruebas de Sensibilidad Microbiana , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Most rotator cuff (RC) tears occur at the bone-tendon interface and cause disability and pain. Farnesol, a sesquiterpene compound, can exert antioxidative and anti-inflammatory effects and promote collagen synthesis. In this rabbit model, either commercial SurgiWrap membrane or hydrogel membranes containing various compositions of gellan gum, hyaluronic acid, and farnesol (hereafter GHF membranes) were applied to the tear site, and the repair of the cuff was examined 2 and 3 weeks afterward. The designed membranes swelled rapidly and adsorbed onto the tear site more readily and closely than the SurgiWrap membrane. The membranes degraded slowly and functioned as both a barrier and a vehicle of slow farnesol release during the repair period. Farnesol enhanced collagen production in myoblasts and tenocytes, and interleukin 6 and tumor necrosis factor α levels were modulated. Gross observations and histological examinations indicated that the GHF membranes impregnated with 4 mM farnesol resulted in superior RC repair. In sum, the slow release of farnesol from hydrogel membranes can be beneficial in the repair of RC injuries.
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Particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5) increases oxidative stress through free radical generation and incomplete volatilization. In addition to affecting the respiratory system, PM2.5 causes aging- and inflammation-related damage to skin. Farnesol (Farn), a natural benzyl semiterpene, possesses anti-inflammatory, antioxidative, and antibacterial properties. However, because of its poor water solubility and cytotoxicity at high concentrations, the biomedical applications of Farn have been limited. This study examined the deleterious effects of PM2.5 on the epidermis and dermis. In addition, Farn-encapsulated liposomes (Lipo-Farn) and gelatin/HA/xanthan gel containing Lipo-Farn were prepared and applied in vivo to repair and alleviate PM2.5-induced damage and inflammation in skin. The prepared Lipo-Farn was 342 ± 90 nm in diameter with an encapsulation rate of 69%; the encapsulation significantly reduced the cytotoxicity of Farn. Lipo-Farn exhibited a slow-release rate of 35% after 192 h of incubation. The half-maximal inhibitory concentration of PM2.5 was approximately 850 µg/mL, and ≥400 µg/mL PM2.5 significantly increased IL-6 production in skin fibroblasts. Severe impairment in the epidermis and hair follicles and moderate impairment in the dermis were found in the groups treated with post-PM2.5 and continuous subcutaneous injection of PM2.5. Acute and chronic inflammation was observed in the skin in both experimental categories in vivo. Treatment with 4 mM Lipo-Farn largely repaired PM2.5-induced injury in the epidermis and dermis, restored injured hair follicles, and alleviated acute and chronic inflammation induced by PM2.5 in rat skin. In addition, treatment with 4 mM pure Farn and 2 mM Lipo-Farn exerted moderate reparative and anti-inflammatory effects on impaired skin. The findings of the current study indicate the therapeutic and protective effects of Lipo-Farn against various injuries caused by PM2.5 in the pilosebaceous units, epidermis, and dermis of skin.
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Dermis/efectos de los fármacos , Epidermis/efectos de los fármacos , Farnesol/farmacología , Liposomas/administración & dosificación , Material Particulado/toxicidad , Sustancias Protectoras/farmacología , Enfermedades de la Piel/tratamiento farmacológico , Animales , Antioxidantes , Dermis/patología , Epidermis/patología , Femenino , Liposomas/química , Ratas , Ratas Sprague-Dawley , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/patologíaRESUMEN
We present a 57-year-old female patient with iatrogenic lateral plantar nerve injury caused by endoscopic surgery for plantar fasciitis. Nerve grafting surgery was recommended, but the patient refused further surgical intervention because of personal reasons. After 1-year follow-up in outpatient clinics, she achieved only slight improvement in the lateral foot symptoms and still required oral analgesics for pain control. The purpose of this case report is to remind physicians of such a rare and serious complication that can occur after endoscopic surgery for plantar fasciitis. Good knowledge of anatomy and skilled surgical technique could decrease this type of complication.
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Fascitis Plantar , Fasciotomía , Fascia , Fascitis Plantar/cirugía , Femenino , Pie , Humanos , Enfermedad Iatrogénica , Persona de Mediana EdadRESUMEN
PURPOSE: This study aimed to develop a quantitative dry cupping system that can monitor negative pressure attenuation and soft tissue pull-up during cupping to quantify soft tissue compliance. METHODS: Baseball players with myofascial pain syndrome were recruited to validate the benefits of cupping therapy. Nine of 40 baseball players on the same team were diagnosed with trapezius myofascial pain syndrome; another nine players from the same team were recruited as controls. All participants received cupping with a negative pressure of 400 mmHg for 15 minutes each time, twice a week, for 4 weeks. Subjective perception was investigated using upper extremity function questionnaires, and soft tissue compliance was quantified objectively by the system. RESULTS: During the 15-minute cupping procedure, pressure attenuation in the normal group was significantly greater than that in the myofascial group (p = 0.017). The soft tissue compliance in the normal group was significantly higher than that in the myofascial group (p = 0.050). Moreover, a 4-week cupping intervention resulted in an obvious increase in soft tissue lift in the myofascial pain group (p = 0.027), although there was no statistical difference in the improvement of soft tissue compliance. Shoulder (p = 0.023) and upper extremity function (p = 0.008) were significantly improved in both groups, but there was no significant difference between the two groups. CONCLUSION: This quantitative cupping monitoring system could immediately assess tissue compliance and facilitate the improvement of soft tissues after cupping therapy. Hence, it can be used in athletes to improve their functional recovery and maintain soft tissues health during the off-season period.
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Atletas , Ventosaterapia , Síndromes del Dolor Miofascial/terapia , Músculos Superficiales de la Espalda/fisiopatología , Adulto , Brazo/fisiopatología , Béisbol , Adaptabilidad , Ventosaterapia/instrumentación , Autoevaluación Diagnóstica , Humanos , Masculino , Presión , Hombro/fisiopatología , Resultado del Tratamiento , Puntos Disparadores/fisiopatología , Adulto JovenRESUMEN
Saikosaponin d (SSd), a primary active component of the Chinese herb Bupleurum falcatum, has antitumor and antiliver fibrosis effects. However, the toxicity of SSd at high doses can induce conditions such as metabolic disorders and hemolysis in vivo, thus hampering its clinical use. The present study investigated the toxicity-reducing effects of liposome encapsulation of pure SSd and the therapeutic action of SSd-loaded liposomes (Lipo-SSd) in liver fibrosis in vitro and in vivo. Lipo-SSd (diameter, 31.7 ± 7.8 nm) was prepared at an entrapment efficiency of 94.1%. After 10-day incubation, a slow release profile of 56% SSd from Lipo-SSd was observed. The IC50 of SSd on hepatic stellate cells was approximately 2.9 µM. Lipo-SSd exhibited much lower cytotoxicity than did pure SSd. In the in vivo toxicity assay, Lipo-SSd significantly increased mice survival rate and duration compared with pure SSd at the same dose. These in vitro and in vivo data indicate that liposomal encapsulation can reduce the cytotoxicity of SSd. The histopathological analysis results demonstrated that in mice with thioacetamide-induced liver fibrosis, Lipo-SSd exerted more obvious fibrosis- and inflammation-alleviating and liver tissue-reparative effects than did pure SSd; these effects are potentially attributable to the sustained release of SSd. In conclusion, Lipo-SSd fabricated here have antiliver fibrosis effects and lower toxicity compared with that of pure SSd.
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Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Cirrosis Hepática Experimental/tratamiento farmacológico , Hígado/efectos de los fármacos , Ácido Oleanólico/análogos & derivados , Sustancias Protectoras/farmacología , Saponinas/farmacología , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Preparaciones de Acción Retardada , Relación Dosis-Respuesta a Droga , Composición de Medicamentos , Liberación de Fármacos , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/patología , Humanos , Concentración 50 Inhibidora , Liposomas , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática Experimental/inducido químicamente , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/patología , Masculino , Ratones Endogámicos C57BL , Ácido Oleanólico/química , Ácido Oleanólico/farmacología , Ácido Oleanólico/toxicidad , Sustancias Protectoras/química , Sustancias Protectoras/toxicidad , Saponinas/química , Saponinas/toxicidad , TioacetamidaRESUMEN
INTRODUCTION: Rapamycin has been considered as a potential treatment for osteoarthritis (OA). Drug carriers fabricated from liposomes can prolong the effects of drugs and reduce side effects of drugs. Low-intensity pulsed ultrasound (LIPUS) has been found to possess anti-OA effects. MATERIALS AND METHODS: The anti-osteoarthritic effects of liposome-encapsulated rapamycin (L-rapa) combined with LIPUS were examined by culture of normal and OA chondrocytes in alginate beads and further validated in OA prone Dunkin-Hartley guinea pigs. RESULTS: L-rapa with LIPUS largely up-regulated aggrecan and type II collagen mRNA in human OA chondrocytes (HOACs). L-rapa with LIPUS caused significant enhancement in proteoglycan and type II collagen production in HOACs. Large decreases in both MMP-13 and IL-6 proteins were found in the HOACs exposed to L-rapa with LIPUS. Intra-articular injection of 40 µL L-rapa at both 5 µM and 50 µM twice a week combined with LIPUS thrice a week for 8 weeks significantly increased GAGs and type II collagen in the cartilage of knee. Results on OARSI score showed that intra-articular injection of 5 µM L-rapa with LIPUS displayed the greatest anti-OA effects. Immunohistochemistry revealed that L-rapa with or without LIPUS predominantly reduced MMP-13 in vivo. The values of complete blood count and serum biochemical examinations remained in the normal ranges after the injections with or without LIPUS. These data indicated that intra-articular injection of L-rapa collaborated with LIPUS is not only effective against OA but a safe OA therapy. CONCLUSION: Taken together, L-rapa combined with LIPUS possessed the most consistently and effectively anabolic and anti-catabolic effects in HOACs and the spontaneous OA guinea pigs. This study evidently revealed that liposome-encapsulation collaborated with LIPUS is able to reduce the effective dose and administration frequency of rapamycin and further stably reinforce its therapeutic actions against OA.
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Osteoartritis/terapia , Sirolimus/uso terapéutico , Ondas Ultrasónicas , Animales , Peso Corporal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Células Cultivadas , Condrocitos/efectos de los fármacos , Condrocitos/patología , Condrocitos/efectos de la radiación , Colágeno Tipo II/metabolismo , Liberación de Fármacos , Cobayas , Humanos , Inyecciones Intraarticulares , Interleucina-6/metabolismo , Liposomas/ultraestructura , Masculino , Metaloproteinasa 13 de la Matriz/metabolismo , Persona de Mediana Edad , Osteoartritis/sangre , Osteoartritis/patología , Proteoglicanos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Sirolimus/administración & dosificación , Sirolimus/farmacologíaRESUMEN
Tibiotalocalcaneal (TTC) arthrodesis with retrograde nail is a widely used treatment option for severe ankle arthropathy. With inherent biomechanical benefits in axial loading and strong bending stiffness, high union rate and good clinical outcomes have been reported in the literature. However, some undesired complications, such as osteomyelitis or implant failure, can develop after this procedure. Herein, we report the case of an 86-year-old man with right ankle osteomyelitis after TTC arthrodesis with retrograde nail. After removing the previous implants and extensive debridement, we used an antibiotic cement nail with multiple screws fixation as a salvage procedure in the same operation. The patient fully recovered without further surgical treatment.
Asunto(s)
Fracturas de Tobillo/terapia , Artritis/cirugía , Artrodesis/métodos , Osteomielitis/terapia , Infecciones Relacionadas con Prótesis/terapia , Anciano de 80 o más Años , Fracturas de Tobillo/complicaciones , Fracturas de Tobillo/cirugía , Articulación del Tobillo/cirugía , Antibacterianos/administración & dosificación , Artritis/etiología , Artrodesis/efectos adversos , Artrodesis/instrumentación , Cementos para Huesos , Clavos Ortopédicos , Tornillos Óseos , Desbridamiento , Remoción de Dispositivos , Humanos , Masculino , Osteomielitis/tratamiento farmacológico , Osteomielitis/etiología , Osteomielitis/cirugía , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/etiología , Infecciones Relacionadas con Prótesis/cirugía , Reoperación , Articulación Talocalcánea/cirugía , Tibia/cirugíaRESUMEN
BACKGROUND: Farnesol is an acyclic sesquiterpene presents in various natural sources including fruits, vegetables, and herbs. In this study, we successfully prepared a farnesol-containing gel with ultraviolet B-screening and skin-repairing capabilities. Furthermore, the advantageous potential of farnesol-containing facial masks for UVB-caused sunburnt skin was evaluated. AIMS: Thus, the objectives of this study are to design and prepare optimal facial masks possessing collagen production and smoothness-enhancing capabilities for the skin. METHODS: A series of formulations consisting of hydroxypropyl methylcellulose, hyaluronan, and farnesol were used to prepare the facial masks. The effects of the facial masks on collagen production by skin fibroblasts in vitro were examined. The effects of the prepared masks on collagen synthesis, smoothness, and inflammation of the skin were further evaluated in vivo using two modes (mask administration interspersed with UVB exposure and mask administration after UVB exposure) of a rat model. RESULTS: Facial masks containing both 0.3 and 0.8 mM farnesol improved skin smoothness and enhanced collagen content and arrangement in the skin of rats with mask administration interspersed with and after UVB exposure. The masks containing 0.8 mM farnesol exerted the greatest effects on collagen production/arrangement and smoothness improvement in vivo model. Histopathologically observed inflammation was alleviated, and interleukin (IL)-6 was decreased in the 0.8 mM farnesol-containing facial mask-covered skin compared with that without facial masks. CONCLUSIONS: The farnesol-containing facial masks prepared in this study may have collagen production-increasing, smoothness-improving, and anti-inflammatory properties for UVB-caused sunburn; thus, farnesol is potentially a beneficial component in facial masks.