Therapeutic Efficacy of Sesquiterpene Farnesol in Treatment of Cutibacterium acnes-Induced Dermal Disorders.

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.

Predicting body composition using foot-to-foot bioelectrical impedance analysis in healthy Asian individuals.

BACKGROUND: The objectives of this study were to develop a regression model for predicting fat-free mass (FFM) in a population of healthy Taiwanese individuals using standing foot-to-foot bioelectrical impedance analysis (BIA) and to test the model's performance in predicting FFM with different body fat percentages (BF%). METHODS: We used dual-energy X-ray absorptiometry (DXA) to measure the FFM of 554 healthy Asian subjects (age, 16-75 y; body mass index, 15.8-43.1 kg/m(2)). We also evaluated the validity of the developed multivariate model using a double cross-validation technique and assessed the accuracy of the model in an all-subjects sample and subgroup samples with different body fat levels. RESULTS: Predictors in the all-subjects multivariate model included height(2)/impedance, weight, year, and sex (FFM = 13.055 + 0.204 weight + 0.394 height(2)/Impedance - 0.136 age + 8.125 sex (sex: Female = 0, Male = 1), r(2) = 0.92, standard error of the estimate = 3.17 kg). The correlation coefficients between predictive FFM by BIA (FFMBIA) and DXA-measured FFM (FFMDXA) in female subjects with a total-subjects BF%DXA of <20 %, 20 %-30 %, 30 %-40 % and >40 % were r = 0.87, 0.90, 0.91, 0.89, and 0.94, respectively, with bias ± 2SD of 0.0 ± 3.0 kg, -2.6 ± 1.7 kg, -1.5 ± 2.8 kg, 0.5 ± 2.7 kg, and 2.0 ± 2.9 kg, respectively. The correlation coefficients between FFMBIA and FFMDXA in male subjects with a total-subjects BF%DXA of <10 %, 10 %-20 %, 20 %-30 %, and >30 % were r = 0.89, 0.89, 0.90, 0.93, and 0.91, respectively, with bias ± 2SD of 0.0 ± 3.2 kg, -2.3 ± 2.5 kg, -0.5 ± 3.2 kg, 0.4 ± 3.1 kg, and 2.1 ± 3.2 kg, respectively. CONCLUSIONS: The standing foot-to-foot BIA method developed in this study can accurately predict FFM in healthy Asian individuals with different levels of body fat.

Study on Anti-Inflammatory Effects of and Muscle Recovery Associated with Transdermal Delivery of Chaenomeles speciosa Extracts Using Supersonic Atomizer on Rat Model.

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.

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.

Restoration of the Phenotype of Dedifferentiated Rabbit Chondrocytes by Sesquiterpene Farnesol.

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.

Enhancement of Rotator Cuff Healing with Farnesol-Impregnated Gellan Gum/Hyaluronic Acid Hydrogel Membranes in a Rabbit Model.

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.

In-room assessment of intravascular velocity from time-resolved rotational angiography in patients with arteriovenous malformation: a pilot study.

BACKGROUND: Time-resolved rotational angiography (t-RA) enables interventionists to better comprehend complex arteriovenous malformations (AVMs), thereby facilitating endovascular treatment. However, its use in evaluating hemodynamic changes has rarely been explored. OBJECTIVE: This study uses t-RA to estimate intravascular flow in patients with AVM to compare this with flow in the normal population. METHODS: Patients with available t-RA scans were prospectively categorized into one of three groups: hemorrhagic AVM, non-hemorrhagic AVM and control. Pulsatile time-density curves (TDCs) for C1, C6 and VOIMCA were used for amplitude and velocity estimation. C1 was at the cervical internal carotid artery (ICA), 2-3 cm below the carotid canal, C6 was at the paraclinoid segment of the ICA, and VOIMCA was at the junction of the first and second segment of the middle cerebral artery (MCA). A waveform amplitude ratio was defined as (peak - trough)/trough contrast intensity. VICA was defined as the distance between C6 and C1 divided by the time required for the wave to pass, and correspondingly, the average velocity of MCA (VMCA) was defined as the distance between C6 and VOIMCA divided by the duration for the same peak to travel from C6 and VOIMCA, AVM volume was estimated by MR angiography. RESULTS: Amplitude ratios AC1 and AC6, and average flow velocities VICA and VMCA were significantly larger in the non-hemorrhagic group than in the control group, while the hemorrhagic AVM group was not significantly different from the controls. VICA and VMCA showed moderate to good correlations with AVM volume (r=0.51 and 0.73, respectively). VMCA (33.0±9.1) was significantly lower than VICA (41.3±13.2) in the control group, but not in the two AVM groups. CONCLUSION: TDC waveform propagation derived from t-RA can quantify hemodynamic differences between AVM and the control group. t-RA provides both real-time anatomic and hemodynamic evaluation, and can thus potentially improve the interventional workflow.