Cepharanthine induces the proliferation of human dermal papilla cells and stimulates vascular endothelial growth factor expression through increased intracellular calcium mobilization and hypoxia-inducible factor activation.

BACKGROUND: Cepharanthine (CEP), a compound extracted from the vine Stephania cephalantha, is commonly prescribed to treat alopecia areata; however, the scientific evidence for its efficacy is limited. AIM: To investigate the effect of CEP and its structural analogues on human hair growth in vitro. METHODS: The effects of CEP and three of its structural analogues on the proliferation of human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs) were investigated. Their effects on vascular endothelial growth factor (VEGF) expression were also assessed by real-time PCR. Activation of pathways leading to VEGF expression, such as intracellular Ca2+ mobilization and hypoxia-inducible factor (HIF) expression, was also characterized. RESULTS: CEP and two of its structural analogues significantly stimulated the growth of hDPCs but not hORSCs. Moreover, CEP and all three structural analogues significantly induced the expression of VEGF in hDPCs. CEP increased the intracellular Ca2+ concentration in hDPCs. CEP also increased the expression of HIF-1α and HIF-2α and induced the expression of HIF-responsive genes in hDPCs, even under normoxia. CONCLUSIONS: These results suggest that CEP and its structural analogues have the potential to restore hair growth by promoting the proliferation of hDPCs and increasing their expression of VEGF.

Carcinosarcoma of the fallopian tube with disappearance of carcinoma cells by neoadjuvant chemotherapy: case study.

The authors report a case of carcinosarcoma (CS) of the fimbria of the fallopian tube in which carcinoma cells disappeared with neoadjuvant chemotherapy (NAC). A 74-year-old woman visited the present hospital with a large pelvic mass and pleural effusion. A magnetic resonance image of the tumor was highly suggestive of ovarian carcinoma. Due to the presence of both serous.adenocarcinoma cells in pleural effusion and pulmonary thrombosis, the patient was given NAC consisting of carboplatin plus paclitaxel (TC) and anticoagulant therapy with warfarin potassium. With six courses of NAC, the pleural effusion and pulmonary thrombosis disappeared, and the tumor decreased 36.2% in greatest diameter. Maximum debulking surgery was then performed. The tumor was found to be located in the fimbria of the right fallopian tube. Hysterectomy and bilateral salpingo-oophorectomy were performed, and histologic examination revealed chondrosarcoma with the presence of necrotic epithelial cells. The necrotic areas were interspersed with papillary structures, and immunohistochemical study showed positivity for CK7 and negativity for CK20, p53, and estrogen receptor (ER), indicating serous adenocarcinoma. Thus, heterologous CS with disappearance of viable carcinoma cells by NAC was diagnosed. The patient was given adjuvant chemotherapy consisting of three courses of TC, and there has been no evidence of disease for 20 months. The authors' experience in this case of gynecologic CS indicates that a serous adenocarcinomatous component of tubal CS can be well cured by TC-based NAC.

Insertable pulse cleaning module with a saturable absorber pair and a compensating amplifier for high-intensity ultrashort-pulse lasers.

We demonstrate the performance of an efficient insertable pulse cleaning module (IPCM) that uses a saturable absorber (SA) pair with a compensating multi-pass amplifier. IPCM consists of a first SA, a grating compressor, a second SA, a stretcher and a compensating Ti:sapphire amplifier. It is implemented with a conventional chirped pulse amplification (CPA) Ti:sapphire laser system, resulting in a double CPA system architecture, and suppresses the amplified spontaneous emission (ASE) level of the pulse pedestal by about three orders of magnitude while preserving the output pulse energy and repetition-rate of the overall laser system. The duration of recompressed cleaned pulses is comparable to that obtained without the cleaning module. The effectiveness of the cleaning module is confirmed in laser-driven proton acceleration experiments. At the 10(9) W/cm2 pedestal level, the surface structure and electrical resistivity of an insulator target (100 nm silicon nitride) are preserved prior to the arrival of the intense ultrashort pulse.

Successful treatment for Cronkhite-Canada syndrome with endoscopic mucosal resection and salazosulfapyridine.

A 79-year-old woman was referred to our hospital because numerous polyps were found in her stomach and large intestine at an ambulatory clinic. Although there were no characteristic symptoms or signs of Cronkhite-Canada syndrome (CCS), endoscopic and pathological findings indicated CCS. Moreover, colonoscopy showed two polypoid lesions (Is type), which appeared neoplastic by magnifying observation with image-enhanced endoscopy (IEE), in the ascending colon. Histologically, the resected specimens revealed tubular adenomas arising in the CCS inflammatory polyps. Remarkable remission of the polyps and edematous mucosa in the stomach and colon was seen after 8 months of administration of salazosulfapyridine (SASP) (3 g/day). Another adenoma was detected and removed endoscopically in the sigmoid colon. This is the first report to describe an asymptomatic case of CCS probably detected in the early phase of the disease, by magnifying IEE which enabled detection and treatment for associated colonic adenomas. SASP was effective in eradication of the inflammatory polyposis, and an additional adenoma was successfully found and removed by surveillance colonoscopy thereafter.

Soft-x-ray harmonic comb from relativistic electron spikes.

We demonstrate a new high-order harmonic generation mechanism reaching the "water window" spectral region in experiments with multiterawatt femtosecond lasers irradiating gas jets. A few hundred harmonic orders are resolved, giving µJ/sr pulses. Harmonics are collectively emitted by an oscillating electron spike formed at the joint of the boundaries of a cavity and bow wave created by a relativistically self-focusing laser in underdense plasma. The spike sharpness and stability are explained by catastrophe theory. The mechanism is corroborated by particle-in-cell simulations.

Endoscopic full-thickness resection of a lateral spreading rectal tumor after unplanned injection of dilute hyaluronic acid into the subserosal layer (with video).

A 74-year-old woman underwent colonoscopy for investigation of a liver tumor. A lateral spreading tumor of the non-granular type (LST-NG), 25 mm in diameter, was detected at the rectosigmoid junction. As magnifying image-enhanced colonoscopy suggested a tubulovillous adenoma, endoscopic mucosal resection (EMR) was chosen for removal of the LST-NG. The lesion was effectively and evenly lifted after injection of 0.4% hyaluronic acid diluted with glycerol in the ratio of 1:1. A small amount of indigo-carmine dye was also added for coloration of the plane of resection. The lesion was completely removed en bloc. Although a blue-colored layer was identified in the resection defect, a small amount of a whitish layer was detected above the blue layer. The muscle layer was clearly located on the underside of the resected polyp. A total of 14 endoclips were used to close the defect completely. The patient was successfully treated conservatively without surgery. Histology of the resected specimen showed that it contained a tubulovillous adenoma with the submucosal layer and both layers of the muscularis propria. The surgical margin was free of neoplastic change horizontally and vertically. To the best of our knowledge, this is the first case report of full-thickness resection associated with EMR after unplanned injection of dilute hyaluronic acid into the subserosal layer rather than the intended submucosal layer. We describe how to promptly recognize this complication during colonoscopy, in order to achieve immediate closure of the defect, with the identification of a "mirror target sign" on the colonic wall.

Efficient multi-keV x-ray generation from a high-Z target irradiated with a clean ultra-short laser pulse.

Kα line emissions from Mo and Ag plates were experimentally studied using clean, ultrahigh-intensity femtosecond laser pulses. The absolute yields of Kα x-rays at 17 keV from Mo and 22 keV from Ag were measured as a function of the laser pulse contrast ratio and irradiation intensity. Significantly enhanced Kα yields were obtained for both Mo and Ag by employing high contrast ratios and irradiances. Conversion efficiencies of 4.28×10⁻5/sr for Mo and 4.84×10⁻5/sr for Ag, the highest values obtained to date, were demonstrated with contrast ratios in the range 10⁻¹° to 10⁻¹¹.

Virulence factors of Helicobacter pylori responsible for gastric diseases in Mongolian gerbil.

Helicobacter pylori infection induces various gastroduodenal diseases. We examined the role of two genes, vacA and cagE, in the gastric pathogenesis induced by H. pylori using a long-term (62 wk) animal model. Reportedly, both genes are associated with the virulence of H. pylori: vacA encodes vacuolating cytotoxin, and cagE, with other genes in the cag pathogenicity islands, encodes a type IV secretion system. Mongolian gerbils were challenged in this study by a wild-type TN2 strain and its isogenic mutants of cagE or vacA. The wild-type and vacA mutants induced severe gastritis, whereas cagE mutants induced far milder changes. Gastric ulcer was induced at the highest rate (22/23) by the wild-type TN2, followed by the vacA mutant (19/28). No ulcer was found in the gerbils infected with the cagE mutant (0/27) or in controls (0/27). Intestinal metaplasia was also found in the gerbils infected with the wild-type (14/23) or vacA mutant (15/28). Gastric cancer developed in one gerbil with wild-type infection and in one with vacA mutant infection. In conclusion, the knocking out of the cagE gene deprived wild-type H. pylori of the pathogenicity for gastritis and gastric ulcer, suggesting that the secretion system encoded by cag pathogenicity island genes plays an essential role.

Energy increase in multi-MeV ion acceleration in the interaction of a short pulse laser with a cluster-gas target.

An approach for accelerating ions, with the use of a cluster-gas target and an ultrashort pulse laser of 150-mJ energy and 40-fs duration, is presented. Ions with energy 10-20 MeV per nucleon having a small divergence (full angle) of 3.4 degrees are generated in the forward direction, corresponding to approximately tenfold increase in the ion energies compared to previous experiments using solid targets. It is inferred from a particle-in-cell simulation that the high energy ions are generated at the rear side of the target due to the formation of a strong dipole vortex structure in subcritical density plasmas.

Tbx5 and the retinotectum projection.

Dorsal and ventral aspects of the eye are distinct from the early stages of development. The developing eye cup grows dorsally, and the choroidal fissure is formed on its ventral side. Retinal axons from the dorsal and ventral retina project to the ventral and dorsal tectum, respectively. Misexpression of the Tbx5 gene induced dorsalization of the ventral side of the eye and altered projections of retinal ganglion cell axons. Thus, Tbx5 is involved in eye morphogenesis and is a topographic determinant of the visual projections between retina and tectum.

Spontaneous complete regression of a rectal cancer.

We report a unique case of a biopsy-proven rectal cancer exhibiting spontaneous complete regression in an extremely short period of 3 months. An 80-year-old man visited our hospital because of a positive fecal occult blood test. Colonoscopy showed a sessile polyp, about 25 mm in diameter, in the middle part of the rectum. Instead of endoscopic resection, two endoscopic biopsies were taken for histological evaluation, as an invasive cancer was endoscopically suspected.Well-differentiated invasive adenocarcinoma was revealed, and thus surgical resection was planned. At the second colonoscopy for endoscopic tattooing before surgery, the polyp was found to have unexpectedly developed into a flat lesion. Furthermore, the surgically removed specimen showed that the flat lesion had transformed to a depressed lesion, and surprisingly, no cancerous tissue was detected histologically.

A clinical comparison between dedifferentiated low-grade osteosarcoma and conventional osteosarcoma.

AIMS: The purpose of this study was to clarify the clinical behaviour, prognosis, and optimum treatment of dedifferentiated low-grade osteosarcoma (DLOS) diagnosed based on molecular pathology. PATIENTS AND METHODS: We retrospectively reviewed 13 DLOS patients (six men, seven women; median age 32 years (interquartile range (IQR) 27 to 38)) diagnosed using the following criteria: the histological coexistence of low-grade and high-grade osteosarcoma components in the lesion, and positive immunohistochemistry of mouse double minute 2 homolog (MDM2) and cyclin-dependent kinase 4 (CDK4) associated with MDM2 amplification. These patients were then compared with 51 age-matched consecutive conventional osteosarcoma (COS) patients (33 men, 18 women; median age 25 years (IQR 20 to 38)) regarding their clinicopathological features. RESULTS: The five-year overall survival (OAS) rates in the DLOS and COS patients were 85.7% and 77.1% (p = 0.728), respectively, and the five-year progression-free survival (PFS) rates were 57.7% and 44.9% (p = 0.368), respectively. A total of 12 DLOS patients received chemotherapy largely according to regimens for COS. Among the nine cases with a histological evaluation after chemotherapy, eight showed a poor response, and seven of these had a necrosis rate of < 50%. One DLOS patient developed local recurrence and five developed distant metastases. CONCLUSION: Based on our study of 13 DLOS cases that were strictly defined by histological and molecular means, DLOS showed a poorer response to a standard chemotherapy regimen than COS, while the clinical outcomes were not markedly different. Cite this article: Bone Joint J 2019;101-B:745-752.

Efficacy and safety of endoscopic submucosal dissection for gastric cancer in patients with liver cirrhosis.

Endoscopic submucosal dissection (ESD) has become a widely accepted method for treating gastrointestinal cancer. The aim of this study was to evaluate the efficacy and safety of ESD for gastric cancer in patients with liver cirrhosis. A total of 18 gastric cancers were treated by ESD in 15 patients with cirrhosis. The rate of en bloc resection was 88.9% (16/18). En bloc resection with tumor-free lateral/basal margins (R0 resection) was 77.8% (14/18). Three patients had postoperative bleeding and underwent emergency gastroscopy for hemostasis. No recurrence was observed during the median follow-up of 21.4 months, excluding three patients in whom additional endoscopic resection or surgery was carried out. ESD can be safely performed for gastric cancer in patients with cirrhosis, resulting in a high en bloc resection rate.

Laser ion acceleration via control of the near-critical density target.

Duration-controlled amplified spontaneous emission with an intensity of 10(13) W/cm(2) is used to convert a 7.5-microm -thick polyimide foil into a near-critical plasma, in which the p -polarized, 45-fs , 10(19) -Wcm (2) laser pulse generates 3.8-MeV protons, emitted at some angle between the target normal and the laser propagation direction of 45 degrees . Particle-in-cell simulations reveal that the efficient proton acceleration is due to the generation of a quasistatic magnetic field on the target rear side with magnetic pressure inducing and sustaining a charge separation electrostatic field.

Asymptomatic hypoesthesia of the maxillary alveolar ridge in complete denture wearers.

This study was carried out to investigate the effect of compression induced by complete dentures on the function of the nerves underlying the dentures. The influence of compression induced by complete dentures on nerve function was analysed using current perception threshold (CPT) in 33 complete denture wearers aged 50-80 at Nihon University School of Dentistry (Matsudo, Japan). Based on the age range of the complete denture group, dentate subjects were selected as a control. Because the group characteristics (such as subject age, gender, body mass index) and oral mucosal thickness were not matched, a multiple regression analysis was used to adjust for the influence of heterogeneous characteristics on the CPT. Statistically significant differences were found between subject groups for the nasopalatine and the greater palatine nerve. The results of the study were that complete denture wearers experience asymptomatic hypoesthesia mainly affecting the nasopalatine and greater palatine nerves, but not the infraorbital nerve.

Scintillator-based transverse proton beam profiler for laser-plasma ion sources.

A high repetition rate scintillator-based transverse beam profile diagnostic for laser-plasma accelerated proton beams has been designed and commissioned. The proton beam profiler uses differential filtering to provide coarse energy resolution and a flexible design to allow optimisation for expected beam energy range and trade-off between spatial and energy resolution depending on the application. A plastic scintillator detector, imaged with a standard 12-bit scientific camera, allows data to be taken at a high repetition rate. An algorithm encompassing the scintillator non-linearity is described to estimate the proton spectrum at different spatial locations.

Burst intensification by singularity emitting radiation in multi-stream flows.

Burst Intensification by Singularity Emitting Radiation (BISER) is proposed. Singularities in multi-stream flows of emitting media cause constructive interference of emitted travelling waves, forming extremely localized sources of bright coherent emission. Here we for the first time demonstrate this extreme localization of BISER by direct observation of nano-scale coherent x-ray sources in a laser plasma. The energy emitted into the spectral range from 60 to 100 eV is up to ~100 nJ, corresponding to ~1010 photons. Simulations reveal that these sources emit trains of attosecond x-ray pulses. Our findings establish a new class of bright laboratory sources of electromagnetic radiation. Furthermore, being applicable to travelling waves of any nature (e.g. electromagnetic, gravitational or acoustic), BISER provides a novel framework for creating new emitters and for interpreting observations in many fields of science.

Triterpenoid CDDO-Im downregulates PML/RARalpha expression in acute promyelocytic leukemia cells.

The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) induces differentiation and apoptosis of diverse human tumor cells. In the present study, we examined the effects of the CDDO imidazolide imide (CDDO-Im) on the NB4 acute promyelocytic leukemia (APL) cell line and primary APL cells. The results show that CDDO-Im selectively downregulates expression of the PML/retinoic receptor alpha fusion protein by a caspase-dependent mechanism and sensitizes APL cells to the differentiating effects of all-trans retinoic acid (ATRA). CDDO-Im treatment of APL cells was also associated with disruption of redox balance and activation of the extrinsic apoptotic pathway. In concert with these results, CDDO-Im sensitizes APL cells to arsenic trioxide (ATO)-induced apoptosis. Our findings indicate that CDDO-Im may be effective in the treatment of APL by: (i) downregulation of PML/RARalpha; (ii) enhancement of ATRA-induced differentiation; and (iii) sensitization of ATO-induced APL cell death.

Application of boron-entrapped stealth liposomes to inhibition of growth of tumour cells in the in vivo boron neutron-capture therapy model.

Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between (10)B and thermal neutrons. It is necessary for effective BNCT therapy to accumulate (10)B atoms in the tumour cells. The delivery system consisted of polyethylene-glycol (PEG) binding liposomes (DPPC/cholesterol/DSPC-PEG2000) with an entrapped (10)B-compound and we evaluated the cytotoxic effects of intravenously injected (10)B-PEG-liposomes on human pancreatic carcinoma xenografts in nude mice with thermal neutron irradiation. After thermal neutron irradiation of mice injected with (10)B-PEG-liposomes, growth of AsPC-1 tumours was suppressed relative to controls. Injection of (10)B-PEG-liposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. These results suggest that intravenous injection of (10)B-PEG-liposomes can increase the retention of (10)B atoms by tumour cells, causing suppression of tumour growth in vivo, after thermal neutron irradiation.