Ameliorative Effects of Cumin Extract-Encapsulated Chitosan Nanoparticles on Skeletal Muscle Atrophy and Grip Strength in Streptozotocin-Induced Diabetic Rats.

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.

Reparative Efficacy of Liposome-Encapsulated Oleanolic Acid against Liver Inflammation Induced by Fine Ambient Particulate Matter and Alcohol in Mice.

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.

Transplantation of 3D adipose-derived stem cell/hepatocyte spheroids alleviates chronic hepatic damage in a rat model of thioacetamide-induced liver cirrhosis.

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.

Farnesol-Loaded Liposomes Protect the Epidermis and Dermis from PM2.5-Induced Cutaneous Injury.

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.

Therapeutic and Protective Effects of Liposomal Encapsulation of Astaxanthin in Mice with Alcoholic Liver Fibrosis.

Astaxanthin (Asta) has been demonstrated to possess anti-inflammatory, antitumor, and free radical-clearing activities. However, the poor stability and low water solubility of Asta hamper its bioavailability. The objectives of this study were to fabricate Asta-loaded liposomes (Asta-lipo) and investigate the therapeutic effects of Asta-lipo on alcoholic liver fibrosis in mice. The mice were administered with Asta-lipo or liposomes alone prior to a 3-week dose containing 30% alcohol with or without feeding with a second dose of 30% alcohol. The prepared Asta-lipo of 225.0 ± 58.3 nm in diameter, had an encapsulation efficiency of 98%. A slow release profile of 16.2% Asta from Asta-lipo was observed after a 24-h incubation. Restorative actions against alcoholic liver fibrosis were observed after oral administration of Asta-lipo for 4 weeks. Hepatic repair, followed by a second dose of 30% alcohol, suggested that Asta-lipo exerted protective and reparative effects against liver injuries induced by repeated consumption of alcohol. The changes of serum ALT and AST values were principally in consistence with the histopathologic findings. Asta-lipo exerted rapid and direct effects against repeated alcohol-induced liver disease, whereas Asta-lipo given orally could boost recovery from liver injuries obtained due to previous long-term alcohol use. These data demonstrate that Asta-lipo has applicable protective and therapeutic potential to treat alcohol-induced liver diseases.

Liposome-encapsulated farnesol accelerated tissue repair in third-degree burns on a rat model.

Third-degree or full-thickness burns refer to lesions that extend to the epidermis, dermis, and subcutaneous tissue. The pathophysiology of burn wounds is characterized by tissue inflammation, edema, and hypertrophic scarring. Farnesol is a natural 15-carbon organic compound that possesses many biological effects. We have previously demonstrated that farnesol gel exerts restorative actions on ultraviolet B (UVB)-caused sunburn in vivo. The in vitro results revealed that liposomal farnesol from 0.04mM to 0.8mM significantly enhanced collagen production by murine skin fibroblasts, whereas liposomal farnesol at high (0.8mM) and low concentration (0.04mM) did not show any suppressions on skin fibroblast proliferation. We treated third-degree burns on a rat model with a formulated gel composed of various ratios of 2% hydroxypropyl methylcellulose (HPMC) and 4mM liposomal farnesol for 7 and 14 days. On days 7 and 14 post wounding, histopathological observations revealed that the HPMC:farnesol gel ratios of 1:2 and 2:1 exerted the greatest tissue-repairing effects on the skin after third-degree burns compared with skin untreated or treated with a commercial burn gel and HPMC alone. These findings were consistent with the in vivo quantitative collagen-producing assay, wound healing scoring, and IL-6 Western blot results. These findings demonstrated that the fabricated liposomal farnesol gel is potentially able to promote wound healing after third-degree burns.

Reparative Effects of Astaxanthin-Hyaluronan Nanoaggregates against Retrorsine-CCl4-Induced Liver Fibrosis and Necrosis.

Astaxanthin (Asta), a xanthophyll carotenoid, has been reported to be a strong antioxidative agent and has anti-inflammatory, antitumor and free radical-scavenging activities. However, inadequate stability and water solubility results in its low bioavailability. This study incorporated Asta into hydrophilic hyaluronan nanoparticles (HAn) to produce Asta-HAn aggregates (AHAna) using an electrostatic field system and investigated the restorative effects of AHAna on retrorsine-CCl4-induced liver fibrosis in rats in vivo. Transmission electron microscopy (TEM) revealed that the prepared HAn were approximately 15 ± 2.1 nm in diameter and after the incorporation of Asta into HAn, the size increased to 210-500 nm. The incorporation efficiency of Asta was approximately 93% and approximately 54% of Asta was released after incubation for 18 h. Significant reductions in alanine aminotransferase and aspartate aminotransferase levels were observed after the rats were intraperitoneally injected with AHAna. Histopathological findings revealed the greatest reduction in hepatic fibrosis and hepatocyte necrosis in the rats after 2 weeks of intraperitoneal injection with AHAna, which is consistent with the data acquired from serum biochemical analysis. The restorative effects on liver damage displayed by AHAna in vivo demonstrated that Asta aggregated through HAn incorporation exerts therapeutic effects on liver fibrosis and necrosis.

Intra-abdominal bleeding with hemorrhagic shock: a case of adrenal myelolipoma and review of literature.

Background: Adrenal myelolipoma is an uncommon, benign, and hormonally non-functioning tumor that is composed of mature adipose tissue and normal hematopoietic tissue. Most cases to date are asymptomatic or have epigastric pain. Acute hemorrhage is the most dramatic manifestation of adrenal myelolipoma; though, it is a rare entity. Hemorrhagic shock due to adrenal myelolipoma, to our knowledge, was much less mentioned so far. Persistent bleeding and uncontrollable hypotension are considered to be absolute indications for immediate surgical operation. Case presentation: Herein we presented a 32-year-old male patient with initial symptoms of nausea, vomiting, and epigastric pain progressing to altered consciousness and hypotension during ER course. Hemorrhagic shock due to a giant adrenal myelolipoma, R't was diagnosed. Emergent exploratory laparotomy was executed, and en bloc excision of tumor was done. Conclusion: Adrenal myelolipoma might be diagnosed as a adjunction to other main causes of illness; furthermore, adrenal myelolipoma could be asymptomatic in lifetime. In our case, however, manifesting as hemorrhage shock was challenging to diagnose step by step; instead, maintaining vital organs perfusion and identifying bleeding sources were to be done. Management of myelolipoma should be done on a case-to-case basis.

Noninvasive Shock Wave Treatment for Capsular Contractures After Breast Augmentation: A Rabbit Study.

BACKGROUND: Capsular contracture is the most common complication of breast augmentation. Although numerous procedures are intended to prevent capsular contracture, their efficacy does not satisfy surgeons or patients. In the present study, we used shock waves to develop innovative protocols to treat capsular contracture in rabbits. METHODS: We used shock waves to treat capsular contracture in a rabbit model. Six clinical parameters were evaluated to determine the treatment efficacy of shock waves on the pathological histology of capsular contracture. Dual-flip-angle T1-mapping magnetic resonance imaging was used to confirm the pathological findings. RESULTS: Among the parameters, myxoid change, vascular proliferation, and lymphoplasma cell infiltration around the capsule increased more after treatment than they did in a control group. Capsular thickness, inner thinner collagen layer, and capsule wall collagen deposition decreased after shock wave treatment; only the inner thinner collagen layer and capsule wall collagen deposition changed significantly. The MRI findings for both scar thickness and water content were consistent with pathological biology findings. CONCLUSION: This was the first pilot study and trial to treat capsular contractures using shock waves. We found that shock waves can cause changes in the structure or the composition of capsular contracture. We conclude that the treatment could decrease water content, loosen structure, decrease collagen deposition, and might alleviate scar formation from capsular contracture. We believe that the treatment could be a viable remedy for capsular contractures. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Successful treatment of a pancreatic pseudocyst accompanied by massive hemothorax: a case report.

BACKGROUND: It is rare to encounter massive hemothorax as a complication of pancreatic pseudocyst. In addition, as no obvious hypotension and abdominal discomfort were noted, it was difficult to consider gastrointestinal lesion a possibility. CASE PRESENTATION: A 54-year-old Taiwanese man had tightness on the left side of his chest and shortness of breath for 3 days. He had a history of acute pancreatitis 3 months ago. After history taking and a series of examinations including thoracocentesis and computed tomography of his abdomen and chest, the diagnosis was finally confirmed based on the high amylase levels in his pleural fluid. CONCLUSIONS: Treatment with distal pancreatectomy and splenectomy was subsequently successfully performed. Based on our experience, we briefly discuss the currently available treatment options for pancreatic pseudocyst.

Preliminary study of non-invasive shock wave treatment of capsular contracture after breast implant: animal model.

The incidence rate of capsular contracture after breast implant is about 8% to 12%. Patients would feel extremely uncomfortable after scar formation. Administering oral medications (such as vitamin E and Zafirlukast tablets, etc.) or invasive breast capsulectomy surgery was commonly used for capsular contracture repair in clinical therapy. However, the therapeutic effect is still under investigation. Shock waves can be used to remove soft connective tissue in clinical applications. It has been widely used in orthopedics and rehabilitation. No related research paper about shock wave treatment of capsular contracture has been published yet. It might provide another choice for capsular contracture repair. In order to simulate breast implantation, two silica-gel bags filled with normal saline were implanted into New Zealand rabbit's thighs bilaterally as an animal model. Six weeks later, daily shock wave treatment on the right thigh was performed for six weeks after capsular contractures were formed, while the other thigh was used as a control. Then, magnetic resonance imaging (MRI) was used to compare the difference between treated and un-treated thighs. Afterwards, pathological sections were analyzed to confirm the findings. It has been demonstrated that shock wave treatments are capable of changing the structure and composition of capsular contractures. The structure of scar became myxoid changed or collagen deposition of scar decreased after shock wave treatment, hence, the formation of scars decreased. Increased myxoid and decreased collagen deposition has also been found.

Melioidosis in an urban-dwelling Taiwanese man with splenic abscesses.

We report a case of melioidosis with splenic abscesses caused by Burkholderia pseudomallei in an urban-dwelling, 54-year-old Taiwanese man. The patient presented with prolonged fever and abdominal pain. A splenectomy was performed, followed by successful treatment with ceftazidime and amoxicillin-clavulanate. The patient recovered fully.