Recurrent Vascularizing Keratitis in Infants With Hereditary Mucoepithelial Dysplasia Related to SREBF1 Mutation.

PURPOSE: This study aims to present ophthalmic manifestations of 2 infants with hereditary mucoepithelial dysplasia (HMD) related to SREBF1 mutation over a 5-year period. METHODS: Two female infants with an unremarkable perinatal history were evaluated for photophobia that had been manifest since 3 months after birth and diffuse scalp alopecia. Complete ocular examinations under anesthesia were performed, as well as genetic and systemic workup. RESULTS: Both patients had vascularizing keratitis in both eyes, characterized by the growth of corneal new vessels from the 360 degrees periphery to the center and the formation of stromal leucomatous opacity at the leading edge. The keratitis partially regressed in response to topical corticosteroids and waxed and waned during the 5 years of follow-up. In addition, the loss of scalp hair developed in a cyclical pattern, causing diffuse scalp alopecia in the patients. Rheumatologic, nutritional, and developmental evaluations were within normal ranges. Whole-exome sequencing identified a heterozygous c.1669C>T (p.Arg557Cys) pathogenic variant in the SREBF1 gene associated with HMD in both patients. CONCLUSIONS: In pediatric patients with recurrent vascularizing keratitis and diffuse scalp alopecia starting early in life, HMD should be considered, and genetic tests and collaboration with dermatologists and pediatricians on the diagnosis should be provided.

One-stage reconstruction using a fibula osteocutaneous free flap and an anterolateral thigh free flap for an extensive composite defect after en bloc resection of squamous cell carcinoma on the mouth floor, mandible, and anterior neck: A CARE-compliant case report.

RATIONALE: Although regional metastasis to the lymph nodes is common in advanced oral cancer, extensive local invasion into surrounding structures such as the mandible, skin and soft tissue of the neck, and masticator space is relatively rare. Sometimes surgical treatment cannot be performed and only palliative chemotherapy and radiation therapy are offered to preserve the quality of life of patients with advanced oral cancer. Nevertheless, the surgical resection of tumors remains the most effective treatment. This study presents a case of aggressive mouth floor cancer in which extensive composite defects on the mouth floor, oral mucosa, mandible, skin and soft tissue of the neck caused by tumor resection were reconstructed. PATIENT CONCERNS: A 66-year-old man and a 65-year-old man with no significant personal or family history visited our clinic due to a large and multiple masses on the floor of the mouth and both sides of the neck. DIAGNOSIS: Histopathological evaluation of the biopsy specimen revealed squamous cell carcinoma. INTERVENTIONS: A fibula osteocutaneous free flap and customized titanium plate were used for the intraoral lining. Mandibular reconstruction was performed using a 3D-printed bone model, and an anterolateral thigh free flap was used to resurface the anterior of the neck. OUTCOMES: Reconstruction using this method was successful, and excellent functional and aesthetic outcomes were achieved without cancer recurrence. LESSONS: This study show that the reconstruction of extensive composite defects of the oral mucosa, mandible, and neck soft tissue following surgical resection of mouth floor cancer can be performed in a single-stage operation. Through a single-stage reconstruction, both excellent functional aspects without cancer recurrence and satisfactory aesthetic outcomes can be obtained.

SS-OCT-based ocular biometry in an adult Korean population with cataract.

PURPOSE: To evaluate the characteristics of ocular biometric parameters in adult Korean patients with cataract. SETTING: Department of Ophthalmology, Seoul National University Hospital, Seoul, South Korea. DESIGN: Retrospective case series. METHODS: Ocular biometric values of 5273 eyes of 5273 Korean patients undergoing cataract surgery measured with the IOLMaster 700 at the Seoul National University Hospital between November 2019 and December 2021 were reviewed. RESULTS: A total of 5273 eyes of 5273 Korean patients were analyzed. The mean ± SD age was 66.1 ± 12.8 years, and 62% were female. Overall, age and ocular biometric parameters were correlated with each other. Particularly, age showed a negative correlation with anterior chamber depth (ACD; r = -0.357), axial length (AL; r = -0.344), and posterior keratometry (PK; r = -0.054) and a positive correlation with lens thickness (LT; r = 0.484), angle α ( r = 0.194), total keratometry (TK; r = 0.137), anterior keratometry (AK; r = 0.129), and angle κ ( r = 0.071). AL showed a positive correlation with ACD ( r = 0.503) and PK ( r = 0.339) and a negative correlation with AK ( r = -0.342), TK ( r = -0.334), LT ( r = -0.288), angle α ( r = -0.220), and angle κ ( r = -0.040). With age, anterior and total corneal astigmatism changed from with-the-rule (WTR) to against-the-rule (ATR) astigmatism. Posterior corneal astigmatism was ATR regardless of age; however, the magnitude decreased with age. CONCLUSIONS: Age showed a significant correlation in the order of LT, ACD, and AL. With age, angle α and κ increased, and total corneal astigmatism changes from WTR to ATR, which is mainly affected by changes in anterior corneal astigmatism. AL showed a significant correlation in the order of ACD, AK, PK, and TK. These data are pertinent for improving the result after cataract surgery, especially when using premium intraocular lenses.

MOF/MWCNT-Nanocomposite Manipulates High Selectivity to Gas via Different Adsorption Sites with Varying Electron Affinity: A Study in Methane Detection in Parts-per-Billion.

Metal-organic frameworks (MOFs) present specific adsorption sites with varying electron affinity which are uniquely conducive to selective gas sensing but are typically large-band-gap insulators. On the contrary, multiwall carbon nanotubes (MWCNTs) exhibit superior mesoscopic transport exploiting strong electron correlations among sub-bands below and above the Fermi level at room temperature. We synergize them in a new class of nanocomposites based on zeolitic imidazolate framework-8 (ZIF-8) and report selective sensing of CH4 in ∼10 parts-per-billion (ppb) with a determined limit of detection of ∼0.22 ppb, hitherto unprecedented. The observed selectivity to CH4 over non-polar CO2, polar volatile organic compounds, and moisture has roots in competing electron-sharing mechanisms at its different adsorption sites. This important result provides a significant reference to guide future MOF-related composite research to achieve the best sensing performance. On molecular adsorption, MWCNTs facilitate electrical transport via manipulating the ZIF-8 band gap to show a p-type semiconductor behavior with lower activation energy to induce a measurable resistance change. Excellent repeatability and reversibility are shown. A carbon-engineered MOF composite has the potential to actuate similar selective response to low reactive gases via carrier manipulation in the energy band gap.

Inhibitory Effect of Asplenium incisum on Bacterial Growth, Inflammation, and Osteoclastogenesis.

Background and Objectives:Asplenium incisum, a natural plant, is known to possess numerous pharmacological and biochemical properties. However, the inhibitory effect of A. incisum against Porphyromonas gingivalis and other factors related to periodontal disease have not yet been demonstrated. This study aimed to investigate the potential of A. incisum extract as a phytotherapeutic candidate for improving periodontal diseases by assessing its antibacterial, anti-inflammatory, and anti-osteoclastogenic activities. Materials and Methods: The inhibition of proliferation of P. gingivalis by A. incisum and the sustainability of its antibacterial activity were evaluated in this study. The production of inflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)) and nitric oxide (NO) from lipopolysaccharide-stimulated RAW 264.7 cells was assessed using an enzyme-linked immunosorbent assay. To identify the anti-osteoclastogenic activity, tartrate-resistant acid phosphatase (TRAP) staining and TRAP activity analyses were performed on bone marrow macrophages. Results: The proliferation of P. gingivalis was significantly inhibited by A. incisum (p < 0.001), and the antibacterial activity was sustained for up to 3 days. A. incisum showed anti-inflammatory activities by significantly decreasing the release of TNF-α, IL-6 (p < 0.05), and NO (p < 0.01). In addition, A. incisum significantly suppressed TRAP-positive cells and TRAP activity (at 30 µg/mL, p < 0.01) without causing any cytotoxicity (p > 0.05). Conclusions:A. incisum showed antibacterial, anti-inflammatory, and anti-osteoclastogenic activities, suggesting it has strong therapeutic potential against periodontal diseases.

Tropolone-Bearing Sesquiterpenes from Juniperus chinensis: Structures, Photochemistry and Bioactivity.

The tropolone-bearing sesquiterpenes juniperone A (1) and norjuniperone A (2) were isolated from the folk medicinal plant Juniperus chinensis, and their structures were determined by a combination of spectroscopic and crystallographic methods. Photojuniperones A1 (3) and A2 (4), bearing bicyclo[3,2,0]heptadienones derived from tropolone, were photochemically produced and structurally identified by spectroscopic methods. Predicted by the machine learning-based assay, 1 significantly inhibited the action of tyrosinase. The new compounds also inhibited lipid accumulation and enhanced the extracellular glycerol excretion.

Tunable Young's Moduli of Soft Composites Fabricated from Magnetorheological Materials Containing Microsized Iron Particles.

This study experimentally investigates the field-dependent Young's moduli of soft composites, which are fabricated from two different magnetic-responsive materials; magnetorheological elastomer (MRE) and magnetorheological fluid (MRF). Four factors are selected as the main factors affecting Young's modulus of soft composites: the amount of MRF, the channel pattern, shore hardness and carbonyl iron particle (CIP) concentration of the MRE layer. Five specimens are manufactured to meet the investigation of four factors. Prior to testing, the scanning electron microscopy (SEM) image is taken to check the uniform dispersion of the carbonyl iron particle (CIP) concentration of the MRE layer, and a magnetic circuit is constructed to generate the effective magnetic field to the specimen fixed at the universal tensile test machine. The force-displacement curve is directly measured from the machine and converted to the stress-strain relationship. Thereafter, the Young's modulus is determined from this curve by performing linear regression analysis with respect to the considered factors. The tunability of the Young's moduli of the specimens is calculated based on the experimental results in terms of two performance indicators: the relative percentage difference of Young's modulus according to the magnetic field, and the normalized index independent of the zero-field modulus. In the case of the relative percentage difference, the specimens without MRF are the smallest, and the ones with the highest CIP concentration are the largest. As a result of comparing the normalized index of each factor, the change in shore hardness and channel pattern have little effect on the tunability of Young's moduli, and the amount of MRF injected and CIP concentration of MRE have a large effect. The results of this study are expected to provide basic guidelines for fabricating soft composites whose field-dependent Young's moduli can be tuned by several factors with different effects.

Intense Pulsed Light-Treated Near-Field Electrospun Nanofiber on a Quartz Tuning Fork for Multimodal Gas Sensors.

Accurate and portable gas sensors are required for environmental monitoring, locating leakages, and detecting trace chemical vapors or gases. Although many sensors have been developed, few can rapidly and selectively detect parts per million (ppm) concentration changes. In this work, we fabricate multimodal gas sensors by depositing a single nanocomposite fiber between the prongs of a quartz tuning fork (QTF). The resulting sensors are portable and integrate multimodal approaches by applying both chemo-mechanical sensing for sensitivity and electrochemical sensing for selectivity. Near-field electrospinning (NFES) produces a flexible and semiconductive nanocomposite fiber with ∼500 nm diameter that can be integrated into electronic systems as environmental gas sensors. Intense pulsed light (IPL) and sputter coating improve adhesion of the nanocomposite fiber onto a QTF. Furthermore, IPL offers improved sensing performance due to the higher specific surface area and reduction in polymer content. In this study, hydrogen gas (H2) is chosen as a target gas since it is a common energy source in fuel cell applications and byproduct in chemical reactions. An electrospinning solution containing polyaniline, multiwalled carbon nanotubes, and platinum nanoparticles is used to test H2 gas sensing performance. The resulting multimodal sensors are selective to hydrogen versus other gases and vapors including methane, hexane, toluene, ammonia, ethanol, carbon dioxide, and oxygen. Furthermore, the sensors detect ppm levels of hydrogen gas even in the presence of high humidity that typically hinders gas sensor performance. The development of this sensor leads to a new method for compact and portable multimodal gas sensing.

Effect of Photobiomodulation Therapy (660 nm) on Wound Healing of Rat Skin Infected by Staphylococcus.

Objective: To assess the impact of photobiomodulation (PBM) therapy on healing of infected wounds and document the microscopic findings throughout the recovery process. Background: Previous studies have suggested that PBM accelerates wound healing and reduces inflammation and pain. However, the ideal protocol and ultimate value of PBM treatment for infected wounds are controversial. Materials and methods: Eight-month-old male rats were randomly divided into the control group, the nonirradiation group, or the irradiation group. A 1 cm diameter skin excision was made. The wounds of the nonirradiated and irradiated rats were inoculated with a suspension of Staphylococcus aureus. We then performed 7 days of PBM therapy at a wavelength of 660 nm for 35 min/day. On day 8, the rats were sacrificed for histological assessment. Sections were stained with hematoxylin and eosin, Masson trichrome, and a proliferating cell nuclear antigen (PCNA) kit. Defect diameter was calculated using the Visus Image Analysis System. Results: The irradiated group had more epithelial cells and richer granulation tissue compared to those in the other groups. The irradiation group had a significantly smaller defect size than the nonirradiation group (p < 0.01) and the control group (p < 0.05). The amount of collagen was highest in the irradiation group and was graded as 3, 2, and 3+ in the control, nonirradiation, and irradiation groups, respectively. The percentage of PCNA in the control group was significantly lower than that in the other two groups (p < 0.05). Conclusions: PBM therapy (660 nm) promoted cell proliferation and collagen synthesis, thereby improving the wound healing response to an S. aureus infection.

Thermo-optic control of the longitudinal radiation angle in a silicon-based optical phased array.

We demonstrate longitudinal beam-steering with a 1×16 silicon optical phased array (OPA) using a monochromatic light source and thermo-optic control of the refractive index in the grating radiator region. The refractive index is controlled by forming a series of n-i-n heaters, placing i-regions in each radiator of the OPA. When the biased voltage in the heaters is increased, the refractive index of the radiator region is increased by the thermo-optic effect, and the longitudinal radiation angle is changed according to the Bragg condition. The transversal beam-steering is accomplished by phase control with the phase shifters, which are devised with a p-i-n diode using the electro-optic effect. With these electro-optic p-i-n phase shifters and n-i-n thermo-optic radiators, we achieve a relatively wide 2D beam-steering in a range of 10.0°/45.4° in the longitudinal/transversal directions with a 1.55 µm light source. The tuning efficiency is 0.016°/mW in the longitudinal beam-steering.

Atolypenes, Tricyclic Bacterial Sesterterpenes Discovered Using a Multiplexed In Vitro Cas9-TAR Gene Cluster Refactoring Approach.

Most natural product biosynthetic gene clusters identified in bacterial genomic and metagenomic sequencing efforts are silent under laboratory growth conditions. Here, we describe a scalable biosynthetic gene cluster activation method wherein the gene clusters are disassembled at interoperonic regions in vitro using CRISPR/Cas9 and then reassembled with PCR-amplified, short DNAs, carrying synthetic promoters, using transformation assisted recombination (TAR) in yeast. This simple, cost-effective, and scalable method allows for the simultaneous generation of combinatorial libraries of refactored gene clusters, eliminating the need to understand the transcriptional hierarchy of the silent genes. In two test cases, this in vitro disassembly-TAR reassembly method was used to create collections of promoter-replaced gene clusters that were tested in parallel to identify versions that enabled secondary metabolite production. Activation of the atolypene ( ato) gene cluster led to the characterization of two unprecedented bacterial cyclic sesterterpenes, atolypene A (1) and B (2), which are moderately cytotoxic to human cancer cell lines. This streamlined in vitro disassembly- in vivo reassembly method offers a simplified approach for silent gene cluster refactoring that should facilitate the discovery of natural products from silent gene clusters cloned from either metagenomes or cultured bacteria.

Surgical outcomes of unilateral recession and resection in intermittent exotropia according to forced duction test results.

PURPOSE: To compare the surgical outcomes of unilateral lateral rectus recession-medial rectus resection (RR) according to forced duction test (FDT) results with those of conventional RR in intermittent exotropia. METHODS: A total of 129 patients aged 3 to 10 years with intermittent exotropia who underwent RR between 2006 and 2011 were included. The operator compared the tension of the lateral rectus (LR) between both eyes. When FDT results were asymmetric, RR was performed on the eye with more LR tension. RR was performed on the nondominant eye when FDT results were symmetric. Patients were divided into two groups; one group (n = 64) underwent RR without FDT (RR group) and the other group (n = 65) underwent RR considering FDT results (RR-FDT group). Success, recurrence, reoperation rates and cumulative probabilities of success were evaluated in both groups. Surgical outcome was considered satisfactory if the distance deviation in the primary position was between ≤ 10 PD of exophoria/tropia and ≤ 10 PD of esophoria/tropia. Recurrence was defined as an alignment of > 10 PD of exophoria/tropia, and overcorrection defined as > 10 PD of esophoria/tropia. Reoperation for recurrence was recommended for constant exotropia ≥ 14 PD at distance. RESULTS: The total follow-up periods were 4.4±2.3 years in the RR group, and 3.9±2.0 years in the RR-FDT group (P = .310). In the RR group, 50 patients (78.1%) were successful, 13 patients (20.3%) had recurrence, and 1 patient (1.6%) had overcorrection at 2 years after surgery. In the RR-FDT group, 58 patients (89.2%) were successful, 5 patients (7.7%) had recurrence, and 2 patients (3.1%) were overcorrected. The recurrence rate at 2 years after operation was significantly lower in the RR-FDT group (P = .045). Recurrence rates during the follow-up period were 5.6% per person-year in the RR group and 2.7% per person-year in the RR-FDT group. Reoperation for recurrence was performed on 7 patients (10.8%) in the RR-FDT group and 16 patients (25.0%) in the RR group (P = .035). Postoperative sensory outcomes were similar between both groups. CONCLUSIONS: The forced duction test was useful in reducing the risk of recurrence at 2 years after surgery when RR was performed on the eye with more passive tension of the LR. Intraoperative FDT may be considered to choose which eye to operate on when planning RR in intermittent exotropia.

Spiroketones and a Biphenyl Analog from Stems and Leaves of Larrea nitida and Their Inhibitory Activity against IL-6 Production.

Bioactivity-guided fractionation for the stems of leaves of Larrea nitida Cav., using interleukin-6 (IL-6) inhibitory assay in human mast cells (HMC-1), led to the isolation of three new compounds with an unprecedented skeleton in nature (1-3) and three known compounds (4-6). Their structures were elucidated through extensive spectroscopic analysis. The three new compounds were elucidated as two new spiroketones, nitidaones A (1), and B (2) and one new biphenyl analog, nitidaol (3). The known compounds were identified as nordihydroguaiaretic acid (4), 7,3',4'-tri-O-methylquercetin (5) and ayanin (6). All the isolates were tested for their inhibitory activity against IL-6 production in HMC-1 cells. Of them, compounds 1, 3-6 showed potent anti-inflammatory activity, with IC50 values of 12.8, 17.5, 14.9, 22.9, and 17.8 µM, respectively.

Additive Effect of Oral Steroid with Topical Nonsteroidal Anti-inflammatory Drug for Preventing Cystoid Macular Edema after Cataract Surgery in Patients with Epiretinal Membrane.

PURPOSE: To investigate the additive effect of oral steroid with topical nonsteroidal anti-inflammatory drug (NSAID) on cystoid macular edema (CME) in patients with epiretinal membrane (ERM) after cataract surgery. METHODS: Medical records of subjects who underwent uneventful cataract surgery (n = 1,349) were retrospectively reviewed; among these patients, those with pre-existing ERM (n = 81) were included. Patients were divided into two groups: one group had postoperative administration of oral steroid for 1 week (n = 45) and the other group did not have oral steroid administration (n = 36). Changes in macular thickness and incidence of CME were compared in both groups. Topical NSAIDs were administered in both groups for 1 month postoperatively. Definite CME and probable CME were defined by changes in retinal contour with or without cystoid changes. Change in central macular thickness of more than three standard deviations (≥90.17 µm) was defined as possible CME. Macular thickness was measured at 1 month after the operation by optical coherence tomography. RESULTS: The incidence of definite, probable, and possible CME were 2.22%, 4.44%, and 8.89% with the use of steroid and 2.78%, 5.56%, and 8.33% without steroid, respectively (p = 0.694, p = 0.603, and p = 0.625), and regardless of treatment group, the incidences in these patients were higher compared to incidences in whole subjects (1.26%, 2.30%, and 4.32%; p = 0.048, p = 0.032, and p = 0.038, respectively). The differences in macular thickness were not statistically different between the two groups. Average changes of central foveal thickness in 3 mm and 6 mm zone were 29.29 µm, 35.93 µm, and 38.02 µm with the use of steroid and 32.25 µm, 44.08 µm, and 45.39 µm without steroid (p = 0.747, p = 0.148, and p = 0.077, respectively). CONCLUSIONS: This study suggests that administration of oral steroid may not have a synergistic effect in reduction of CME and retinal thickness in patients with pre-existing ERM after cataract surgery, when topical NSAIDs are applied.

Borrelidins C-E: New Antibacterial Macrolides from a Saltern-Derived Halophilic Nocardiopsis sp.

Chemical investigation of a halophilic actinomycete strain belonging to the genus Nocardiopsis inhabiting a hypersaline saltern led to the discovery of new 18-membered macrolides with nitrile functionality, borrelidins C-E (1-3), along with a previously reported borrelidin (4). The planar structures of borrelidins C-E, which are new members of the rare borrelidin class of antibiotics, were elucidated by NMR, mass, IR, and UV spectroscopic analyses. The configurations of borrelidines C-E were determined by the interpretation of ROESY NMR spectra, J-based configuration analysis, a modified Mosher's method, and CD spectroscopic analysis. Borrelidins C and D displayed inhibitory activity, particularly against the Gram-negative pathogen Salmonella enterica, and moderate cytotoxicity against the SNU638 and K562 carcinoma cell lines.

Asperphenins A and B, Lipopeptidyl Benzophenones from a Marine-Derived Aspergillus sp. Fungus.

Asperphenins A (1) and B (2), novel diastereomeric lipopeptidyl benzophenone metabolites, were isolated from a marine-derived Aspergillus sp. fungus. On the basis of the results of combined spectroscopic analyses, the structures of these compounds were determined to be linear assemblies of three motifs: a hydroxy fatty acid, a tripeptide, and a trihydroxybenzophenone. The absolute configurations were assigned using chemical modifications and electronic circular dichroism (ECD) calculations. The novel compounds exhibited significant cytotoxicity on diverse cancer cells.

Effects of senofilcon A mechanical protector on corneal endothelial cells during phacoemulsification in rabbit eyes: Pilot study.

PURPOSE: To evaluate the effects of a senofilcon A mechanical protector against corneal endothelial cell damage induced by phacoemulsification in rabbit eyes. SETTING: Department of Ophthalmology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, South Korea. DESIGN: Experimental study. METHODS: The endothelial cell count, intraocular pressure (IOP), and central corneal thickness (CCT) were measured before and 3 days after the experiment in 26 rabbit eyes randomized into a test group and control group (6 per group). In study 1, a senofilcon A mechanical protector was inserted into the anterior chamber in the hard-shell group (test group) whereas, an ophthalmic viscosurgical device (OVD) was injected in the cohesive group (control group). Phacoemulsification was performed for a total of 5 minutes (10-second intervals). In study 2, the soft-shell technique was used in the control group with 5 minutes of continuous phacoemulsification. In 2 eyes, the safety and toxicity of the mechanical protector were evaluated. RESULTS: In study 1, there was a 4% loss of endothelial cells associated with the mechanical protector and an 18% loss after phacoemulsification in eyes injected with an OVD; the difference between them was not statistically significant (P = .394). The IOP and CCT also showed nonsignificant differences in both studies. In study 2, the hard-shell technique induced significantly less endothelial cell damage than the soft-shell group (P = .026). Endothelial cell loss caused by the mechanical protector was negligible. CONCLUSION: The senofilcon A mechanical protector had a protective effect against corneal endothelial cell damage during phacoemulsification in rabbits.

Meroterpenoids from a Tropical Dysidea sp. Sponge.

Six new meroterpenoids (1-6), along with arenarol (7), a known rearranged drimane sesquiterpene hydroquinone, were isolated from a Dysidea sp. sponge collected from the Federated States of Micronesia. On the basis of the results of combined spectroscopic analysis, compound 1 was determined to be the cyclic ether derivative of 7, whereas 2 and 3 were assigned as the corresponding sesquiterpene quinones containing taurine-derived substituents. Compounds 4-6 possess a novel tetracyclic skeleton formed by a direct linkage between the quinone and sesquiterpene moieties. The configurations of these new compounds were assigned on the basis of combined NOESY and ECD analysis. These compounds exhibited cytotoxic and antimicrobial activities and weak inhibition against Na(+)/K(+)-ATPase.

Salternamide A Suppresses Hypoxia-Induced Accumulation of HIF-1α and Induces Apoptosis in Human Colorectal Cancer Cells.

Hypoxia inducible factor-1α (HIF-1α) is an essential regulator of the cellular response to low oxygen concentrations, activating a broad range of genes that provide adaptive responses to oxygen deprivation. HIF-1α is overexpressed in various cancers and therefore represents a considerable chemotherapeutic target. Salternamide A (SA), a novel small molecule that is isolated from a halophilic Streptomyces sp., is a potent cytotoxic agent against a variety of human cancer cell lines. However, the mechanisms by which SA inhibits tumor growth remain to be elucidated. In the present study, we demonstrate that SA efficiently inhibits the hypoxia-induced accumulation of HIF-1α in a time- and concentration-dependent manner in various human cancer cells. In addition, SA suppresses the upstream signaling of HIF-1α, such as PI3K/Akt/mTOR, p42/p44 MAPK, and STAT3 signaling under hypoxic conditions. Furthermore, we found that SA induces cell death by stimulating G2/M cell cycle arrest and apoptosis in human colorectal cancer cells. Taken together, SA was identified as a novel small molecule HIF-1α inhibitor from marine natural products and is potentially a leading candidate in the development of anticancer agents.

The safety and efficacy of percutaneous transhepatic gallbladder drainage in elderly patients with acute cholecystitis before laparoscopic cholecystectomy.

PURPOSE: Laparoscopic cholecystectomy (LC) is the standard management for acute cholecystitis. Percutaneous transhepatic gallbladder drainage (PTGBD) may be an alternative interim strategy before surgery in elderly patients with comorbidities. This study was designed to evaluate the safety and efficacy of PTGBD for elderly patients (>60 years) with acute cholecystitis. METHODS: We reviewed consecutive patients diagnosed with acute cholecystitis between January 2009 and December 2013. Group I included patients who underwent PTGBD, and patients of group II did not undergo PTGBD before LC. RESULTS: All 116 patients (72.7 ± 7.1 years) were analyzed. The preoperative details of group I (n = 39) and group II (n = 77) were not significantly different. There was no significant difference in operative time (P = 0.057) and intraoperative estimated blood loss (P = 0.291). The rate of conversion to open operation of group I was significantly lower than that of group II (12.8% vs. 32.5%, P < 0.050). No significant difference of postoperative morbidity was found between the two groups (25.6% vs. 26.0%, P = 0.969). In addition, perioperative mortality was not significantly different. Preoperative hospital stay of group I was significantly longer than that of group II (10.3 ± 5.7 days vs. 4.4 ± 2.8 days, P < 0.050). However, two groups were not significantly different in total hospital stay (16.3 ± 9.0 days vs. 13.4 ± 6.5 days, P = 0.074). CONCLUSION: PTGBD is a proper preoperative management before LC for elderly patients with acute cholecystitis.