MAPK/AP-1 Signaling Pathway Is Involved in the Protection Mechanism of Bone Marrow Mesenchymal Stem Cells-Derived Exosomes against Ultraviolet-Induced Photoaging in Human Dermal Fibroblasts.

INTRODUCTION: The role of bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exo) in skin photoaging was explored in human dermal fibroblasts (HDFs). The underlying mechanism was further explored. METHODS: HDFs were exposed to UVB irradiation to establish the cell photodamage models. The cell viability and levels of oxidative stress-related factors were tested. ELISA was done to detect TNF-α, IL-6, and IL-1ß concentrations. Western blot was applied for protein examination. RESULTS: UVB treatment led to the inhibition of cell viability. But after BMSCs-exo addition, the inhibitory effect was returned in a dose manner. UVB exposure contributed to the increase of reactive oxygen species and LDH and the downregulation of superoxide dismutase. In addition, excessive secretion of TNF-α, IL-6, and IL-1ß was also detected in cells exposed to UVB. However, BMSCs-exo addition eliminated the effects of UVB on oxidative stress and inflammation in HDFs. BMSCs-exo inhibited matrix metalloproteinases MMP-1 and MMP-3 expression but promoted collagen I expression. UVB radiation activated the MAPK/AP-1 signaling, manifested as the increase of p-p38, c-Jun, and c-Fos protein levels, which were reversed by BMSCs-exo. As a p38 agonist, anisomycin counteracted the effect of BMSCs-exo on HDF's viability, oxidative stress, and inflammation. CONCLUSION: BMSCs-exo protected HDFs against UVB-induced inhibition of cell viability and the activation of cell oxidative stress and inflammation, which might be related to the inhibition of the MAPK/AP-1 signaling pathway.

Bone marrow mesenchymal stem cell-derived exosome miR-29b-3p alleviates UV irradiation-induced photoaging in skin fibroblast.

BACKGROUND: Mesenchymal stem cells-derived exosome (MSCs-exo) was identified to reduce photoaging. The purpose of this study was to investigate the potential role of microRNA (miR)-29b-3p derived from bone marrow MSCs-exo (BMSCs-exo) in photoaging. METHODS: Exosomes were isolated from BMSCs and verified by Western blot. A photoaging cell model was constructed by UVB irradiation of human dermal fibroblasts (HDFs). Quantitative real-time PCR (RT-qPCR) was performed to detect the mRNA levels of miR-29b-3p, collagen type I and matrix metalloproteinases (MMPs). CCK-8, Transwell and flow cytometry were applicated to examine cell viability, migration and apoptosis. Commercial kits are used to measure levels of oxidative stress indicators. Finally, a dual-luciferase reporter assay was applied to validate the target of miR-29b-3p. RESULTS: Extracted exosomes were positive for HSP70 and CD9. Survival of HDFs increased in an exosome concentration-dependent manner. UVB irradiation inhibited miR-29b-3p levels compared with controls, but BMSCs-exo treatment restored miR-29b-3p levels (p < .05). Additionally, BMSCs-exo-miR-29b-3p reversed the inhibition of HDFs migration and oxidative stress by UVB irradiation, as well as the promotion of apoptosis. However, this reversal was attenuated by the suppression of miR-29b-3p (p < .05). Furthermore, BMSCs-exo-miR-29b-3p also inhibited the degradation of collagen type I and the production of MMPs in photoaging, and they were also eliminated by the reduced miR-29b-3p. Finally, MMP-2 was the target gene of miR-29b-3p. CONCLUSION: Our study presented a novel role for BMSCs-exo-miR-29b-3p in improving skin photoaging function, and these findings may provide new insights into the targeted treatment of skin photoaging.

Cancer overdiagnosis: a challenge in the era of screening.

"Screening" is a search for preclinical, asymptomatic disease, including cancer. Widespread cancer screening has led to large increases in early-stage cancers and pre-cancers. Ubiquitous public messages emphasize the potential benefits to screening for these lesions based on the underlying assumption that treating cancer at early stages before spread to other organs should make it easier to treat and cure, using more tolerable interventions. The intuition is so strong that public campaigns are sometimes launched without conducting definitive trials directly comparing screening to usual care. An effective cancer screening test should not only increase the incidence of early-stage preclinical disease but should also decrease the incidence of advanced and metastatic cancer, as well as a subsequent decrease in cancer-related mortality. Otherwise, screening efforts may be uncovering a reservoir of non-progressive and very slowly progressive lesions that were not destined to cause symptoms or suffering during the person's remaining natural lifespan: a phenomenon known as "overdiagnosis." We provide here a qualitative review of cancer overdiagnosis and discuss specific examples due to extensive population-based screening, including neuroblastoma, prostate cancer, thyroid cancer, lung cancer, melanoma, and breast cancer. The harms of unnecessary diagnosis and cancer therapy call for a balanced presentation to people considering undergoing screening, even with a test of accepted benefit, with a goal of informed decision-making. We also discuss proposed strategies to mitigate the adverse sequelae of overdiagnosis.

Efficient fabrication of tilt micro/nanopillars on polypropylene surface with robust superhydrophobicity for directional water droplet rebound.

The directional rebound and transport of water droplets plays an important role in microfluidic devices, anti-fogging, and water harvesting. Herein, an extrusion compression molding and directional stretch demolding method was used to prepare a polypropylene (PP) surface with tilt micro/nanopillars with a contact angle of 157 ± 3°. The rolling angle is the highest (9 ± 4°) when the direction of rotation is opposite the tilt direction of the micro/nanopillars, showing excellent water repellency and anisotropy of the surface. Compared with the position of the first collision of the water droplet, the position of the second collision shifted ∼1.5 mm along the tilt direction of the micro/nanopillars, driven by the surface tension component during the collision. The directional rebound behavior is controlled by the droplet energy and the tilt angle. The micro/nanopillars demonstrate excellent self-cleaning property and mechanical durability, which shows the possibility of their practical engineering applications.

Bioinspired Micro/Nanostructured Polyethylene/Poly(Ethylene Oxide)/Graphene Films with Robust Superhydrophobicity and Excellent Antireflectivity for Solar-Thermal Power Generation, Thermal Management, and Afterheat Utilization.

The rational utilization and circulation of multiple energy sources is an effective way to address the crises of energy shortages and environmental pollution. Herein, microextrusion compression molding, an industrialized polymer molding technology that combines melt blending and compression molding, is proposed for the mass production of a bioinspired micro/nanostructured polyethylene/poly(ethylene oxide)/graphene (MN-PPG) film. The MN-PPG film exhibits robust shape stability, high storage energy density, and excellent thermal management capability owing to the cocontinuous network formed by poly(ethylene oxide) and the polyethylene matrix. The MN-PPG film has sufficient photothermal property due to the uniformly dispersed graphene nanosheets and the bioinspired surface micro/nanostructures. Interestingly, the MN-PPG film surface exhibits durable superhydrophobicity, acid/alkali resistance, and active deicing performance. Further, a multifunctional energy harvesting and circulation system was established by integrating the MN-PPG film, an LED chip, and a thermoelectric module. The hybrid system produced an open-circuit voltage of 315.4 mV and power output of 2.5 W m-2 under 3 sun irradiation. Furthermore, the afterheat generated by the LED chips at night can be converted into electricity through thermoelectric conversion. The proposed method enables the large-scale fabrication of multifunctional phase change composites for energy harvesting in harsh environments.

Mechanisms of Resistance to Spot Blotch in Yunnan Iron Shell Wheat Based on Metabolome and Transcriptomics.

Spot blotch (SB) is a fungal disease that threatens wheat yield and quality. Presently, the molecular mechanism against SB is unclear. In this study, the resistant variety Zhenkang iron shell wheat (Yunmai 0030) and susceptible variety Lincang iron shell wheat (Yunmai 0608) were selected by identifying SB of Yunnan iron shell wheat. The metabolome and transcriptome of leaves of two varieties at different positions were detected using the systemic acquired resistance theory to investigate the molecular and physiological changes in Yunnan iron shell wheat under SB stress. We found that the genes and metabolites related to benzoxazinoid biosynthesis and arginine and proline metabolism were highly enriched after infection with leaf blight. The enriched differential metabolites mainly included phenolic acids, alkaloids, and flavonoids. We further observed that DIBOA- and DIMBOA-glucoside positively affected iron shell wheat resistance to leaf blight and proline and its derivatives were important for plant self-defense. Furthermore, we confirmed that the related metabolites in benzoxazinoid biosynthesis and arginine and proline metabolism positively affected Triticum aestivum ssp. resistance to SB. This study provides new insights into the dynamic physiological changes of wheat in response to SB, helps us better understand the mechanism of resistance to SB, and contributes to the breeding and utilization of resistant varieties.

Tunable fabrication of biomimetic polypropylene nanopillars with robust superhydrophobicity and antireflectivity.

The fine nanopillars on the natural cicada wing, which exhibits outstanding superhydrophobicity and anti-reflectivity, are carefully observed and analyzed. Here, a promising strategy by combining anodic aluminum oxide template and hot embossing is proposed for rapidly and efficiently mimicking the orderly and densely arranged nanopillars on the cicada wing surface to polypropylene (PP) surfaces. By adjusting the compression pressure, the nanostructures on the PP replica surface gradually evolve from nanoprotrusion-like features to nanopillar-like features so that a gradient wetting behavior from hydrophilicity to hydrophobicity and further to superhydrophobicity appears on the PP replica surfaces. Specifically, the biomimetic PP replica surface exhibits a contact angle of 159 ± 3° and a rolling angle of 8 ± 3° at a compression pressure of 15 MPa. Moreover, the biomimetic PP replica surface can stabilize its superhydrophobic state under a 1.96 kPa external pressure during the dynamic droplet impact. Besides robust dynamic superhydrophobicity, the biomimetic PP replica surface also demonstrated excellent anti-reflectivity because of the gradually changed effective refractive index. Therefore, the biomimetic PP replica inherits both the superhydrophobicity and anti-reflectivity of the natural cicada wing, which makes the products can effectively reduce the external damage when applied to agricultural films, dustproof films, and packaging materials.

Added Diagnostic Utility of Clinical Metagenomics for the Diagnosis of Pneumonia in Immunocompromised Adults.

BACKGROUND: In the evaluation of community-acquired pneumonia, 30% to 60% of cases remain undiagnosed, despite extensive conventional microbiologic testing (CMT). Clinical metagenomics (CM) is an unbiased pathogen detection method that can increase diagnostic yield. RESEARCH QUESTION: Does adding clinical metagenomics to conventional microbiologic testing improve the diagnostic yield for pneumonia in immunocompromised adults? STUDY DESIGN AND METHODS: We performed a noninterventional prospective study of immunocompromised adults with pneumonia who underwent bronchoscopy and BAL over 2 years. CMT was performed per standard of care. A commercial CM test was performed on residual BAL fluid. Final microbiologic diagnoses were based on CMT vs CMT + CM. Final clinical diagnoses for CMT and CMT + CM were made based on laboratory results in conjunction with clinical and radiologic findings. Hypothetical impact of CMT + CM on management and antimicrobial stewardship was also assessed. RESULTS: A total of 30 immunocompromised adult patients (31 episodes of pneumonia) were included. Final microbiologic diagnoses were made in 11 cases (35%) with the use of CMT and in 18 cases (58%) with the use of CMT + CM. Bacterial pneumonia was diagnosed in five cases (16%) by CMT and in 13 cases (42%) by CMT + CM; fungal pneumonia was diagnosed in six cases (19%) by CMT and in seven cases (23%) by CMT + CM, and viral pneumonia was diagnosed in two cases (6%) by CMT and in five cases (16%) by CMT + CM. The hypothetical impact of CMT + CM on management was deemed probable in one case, possible in eight cases, and unlikely in two cases, whereas the impact on antimicrobial stewardship was possible in 13 cases and unlikely in seven cases. Final clinical diagnoses were made in 20 of 31 cases (65%) based on CMT and in 23 of 31 cases (74%) based on CMT + CM. INTERPRETATION: CMT + CM increased diagnostic yield in immunocompromised adults with pneumonia from 35% to 58%, mostly by the detection of additional bacterial causes but was less useful for fungal pneumonia.

Random vibration-driven continuous-wave CRDS system for calibration-free gas concentration measurement.

Random vibrations were employed to pick up each monochromatic component in a continuous-wave cavity ringdown spectroscopy (CRDS) system using a bichromatic laser source. Light frequencies were selected within flat portions of an absorption profile to suppress the jitter in laser frequency during measurements. An interference effect caused by cavity length variations was suppressed by optimizing the initial fit point for each ringdown transient. The difference in exponential decay rates of two frequencies determined the gas mole fraction, and no calibration of empty cavity losses was necessary. Experiments on varying humidity were conducted, and the results agreed with the readings of a commercial hygrometer.

The Human Skin-Derived Precursors for Regenerative Medicine: Current State, Challenges, and Perspectives.

Skin-derived precursors (SKPs) are an adult stem cell source with self-renewal and multipotent differentiation. Although rodent SKPs have been discussed in detail in substantial studies, human SKPs (hSKPs) are rarely reported. Understanding the biological properties and possible mechanisms underlying hSKPs has important implications for regenerative medicine particularly clinical applications, as human-derived sources are more suitable for clinical transplantation. The finding that hSKPs derivatives, such as neural and mesodermal progeny, have both in vitro and in vivo function without any genetical modification makes hSKPs a trustable, secure, and accessible resource for cell-based therapy. Here, we provide an overview of hSKPs, describing their characteristics, originations and niches, and potential applications. A comparison between traditional and innovative culture methods used for hSKPs is also introduced. Furthermore, we discuss the challenges and the future perspectives towards the field of hSKPs. With this review, we hope to point out the current stage of hSKPs and highlight the problems that remain in this field.

Whole genome sequencing and 6-year follow-up of a mother and daughter with frontometaphyseal dysplasia associated with keratitis, xerosis, poikiloderma, and acro-osteolysis: A case report.

RATIONALE: Frontometaphyseal dysplasia (FMD) is a dominant X-linked rare disease caused by mutations of FLNA. The distinctive features of FMD include skeletal dysplasia, facial dysmorphism, extremities anomalies, deafness, cleft palate and eye anterior segment anomalies, yet none of the complications, such as acro-osteolysis, keratitis, xerosis or poikiloderma, have been reported in FMD. PATIENT CONCERNS: A 29-year-old mother and her 7-year-old daughter, both presented with congenital glaucoma, craniofacial dysmorphism, xerosis and poikiloderma, were admitted to our hospital in 2011. Additionally, the mother also suffered from acro-osteolysis, keratitis, camptodactyly of hands and metastatic cutaneous squamous cell carcinoma (SCC) which turned out to be fatal 5 years later. In 2017, keratitis and acro-osteolysis were noticed in the daughter as well. Radiography showed bowed long bones with thickening cortex, and distal phalangeal osteolysis. DIAGNOSES: Whole genome sequencing (WGS) was conducted in 2016, resulting in 71491 single-nucleotide polymorphisms and 7616 indels shared by patients while the father was taken as control. A FLNA variant was classified likely pathogenic, supporting the diagnoses of FMD. In addition, though our patients' symptoms were highly consistent with xeroderma pigmentosum variant, a mild subtype of xeroderma pigmentosum (XP) with merely accumulated UV-induced lesions like xerosis and poikiloderma limited to sun-exposure sites, higher risks of cutaneous neoplasms and absence of classical XP features, WGS didn't find supportive genetical evidence, but 2 HERC2 variants were assigned highest suspicion in both XP and SCC by bioinformatical analyses. INTERVENTIONS: Anti-inflammatory treatment, sunscreens and moisturizers were administered. OUTCOMES: The daughter's cutaneous lesions developed slowly during the 6-year follow-up, but the keratitis seriously weakened her sight. LESSONS: To our knowledge, it's the first report of cases carrying FMD, keratitis, xerosis, poikiloderma and acro-osteolysis simultaneously, and 3 likely pathogenic variants were identified. Whole genome/exon sequencing is recommended as a common test for patients with rare phenotypes.

The efficacy and safety of the fractional radiofrequency technique for the treatment of atrophic acne scar in Asians: A meta-analysis.

BACKGROUND: The fractional radiofrequency (fRF) technique is a recently emerged technique. However, the exact outcomes of fRF for treating atrophic acne scar in Asians are still unclear. OBJECTIVE: To compare the clinical outcomes of fRF with the fractional laser technique in Asians with atrophic acne scar. MATERIALS AND METHODS: The databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Chinese National Knowledge Infrastructure (CNKI) were searched. Main clinical outcomes were participant-reported scar improvement, investigator-reported scar improvement, post-inflammatory hyperpigmentation (PIH), erythema duration, scab duration, and the pain level. RESULT: Six randomized controlled trials were included in this meta-analysis. The scar improvement was similar in both groups regarding participant-reported scar improvement (p = 0.48) and investigator-reported scar improvement (p = 0.89). However, the incidence of PIH in fRF group was lower in comparison with the laser group (p < 0.001). The average duration of erythema was shorter in fRF group than in the laser group (p < 0.001). The mean time for debridement was shorter in fRF group than the carbon dioxide fractional laser system (p = 0.02). The pain level did not differ significantly in the two groups (p = 0.53). CONCLUSION: Although some bias exists in our study, fRF appears to be a superior alternative for the treatment of atrophic acne scar in Asians.

Vitiligo: How do oxidative stress-induced autoantigens trigger autoimmunity?

Vitiligo is a common depigmentation disorder characterized by a loss of functional melanocytes and melanin from epidermis, in which the autoantigens and subsequent autoimmunity caused by oxidative stress play significant roles according to hypotheses. Various factors lead to reactive oxygen species (ROS) overproduction in the melanocytes of vitiligo: the exogenous and endogenous stimuli that cause ROS production, low levels of enzymatic and non-enzymatic antioxidants, disturbed antioxidant pathways and polymorphisms of ROS-associated genes. These factors synergistically contribute to the accumulation of ROS in melanocytes, finally leading to melanocyte damage and the production of autoantigens through the following ways: apoptosis, accumulation of misfolded peptides and cytokines induced by endoplasmic reticulum stress as well as the sustained unfolded protein response, and an 'eat me' signal for phagocytic cells triggered by calreticulin. Subsequently, autoantigens presentation and dendritic cells maturation occurred mediated by the release of antigen-containing exosomes, adenosine triphosphate and melanosomal autophagy. With the involvement of inducible heat shock protein 70, cellular immunity targeting autoantigens takes the essential place in the destruction of melanocytes, which eventually results in vitiligo. Several treatments, such as narrow band ultraviolet, quercetin and α-melanophore-stimulating hormone, are reported to be able to lower ROS thereby achieving repigmentation in vitiligo. In therapies targeting autoimmunity, restore of regulatory T cells is absorbing attention, in which narrow band ultraviolet also plays a role.

[Protective effect of Pinus massoniana bark extracts against cisplatin-induced nephrotoxicity in human embryonic kidney cells].

OBJECTIVE: To investigate the in vitro protective effect of Pinus massoniana bark extracts (PMBE) against cisplatin-induced nephrotoxicity in human embryonic kidney cells (HEK293), and preliminarily study its mechanism. METHOD: Human embryonic kidney cells (HEK293) were cultured in vitro. The MTT assay was adopted to test the effect of PMBE and cisplatin on growth of HEK293 cells, and the protective effect of PMBE on cisplatin-induced nephrotoxicity of HEK293, and then detect the intracellular reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) content, catalase (CAT), superoxide dismutase (SOD) and activity of thioredoxin reductase (TrxR). RESULT: PMBE could promote growth of HEK293 cells at low concentrations, but generate slight nephrotoxicity at high concentration. Cisplatin could inhibit growth of HEK293 cells, increase ROS and MDA content, while reducing SOD, CAT and TrxR. The pre-protective PMBE was added to reduce cisplatin's injury to HEK293 cells, ROS, MDA and GSH content, SOD, CAT and TrxR within certain range. CONCLUSION: PMBE at specific concentration has the protective effect in cisplatin-induced nephrotoxicity in HEK293 cells. Its mechanism may be related to PMBE's antioxidant activity.

Expression of genes encoding cytokines and corticotropin releasing factor are altered by citalopram in the hypothalamus of post-stroke depression rats.

OBJECTIVES: To establish a rat model of post-stroke depression (PSD), and examine expression of genes encoding corticotropin releasing factor (CRF), interleukin 1 beta (IL-1ß), and tumor necrosis factor alpha (TNF-α) in the hypothalamus of PSD rats. METHODS: Rats were subjected to middle cerebral artery occlusion (MCAO) and chronic mild unpredictable stress (CUMS). Open field test and sucrose preference were used to examine depressive-like behaviors. Observed changes in gene expression levels in the hypothalamus of PSD rats were evaluated. RESULTS: MCAO with CUMS resulted in reduction of sucrose preference and locomotor activity. Genes encoding TNF-α, IL-1ß and CRF were highly expressed in the hypothalamus of rats subjected to MCAO and CUMS. The antidepressant citalopram, a selective serotonin reuptake inhibitor, had inhibitory effects on the expression of the aforementioned genes. We observed a correlation between CRF and IL-1ß mRNA levels in the citalopram-treated group of rats. CONCLUSION: The etiology of PSD is associated with cytokine expression in the hypothalamus and with hypothalamic-pituitary-adrenal axis activity. Citalopram administration inhibited the expression of TNF-α and IL-1ß transcripts in the hypothalamus, suggesting that selective serotonin reuptake inhibitors may be appropriate for PSD therapy.

Antitumor effects of Pinus massoniana bark extract in murine sarcoma S180 both in vitro and in vivo.

Pinus massoniana bark extract (PMBE) is a mixture of flavonoids, and showed a capability of inducing cell apoptosis; however, its properties have not yet been fully investigated. This paper evaluates the antitumor effects of PMBE in murine sarcoma S180 both in vitro and in vivo. In vitro, the growth inhibition of S180 cells was concentration dependent on PMBE as shown by the CCK-8 assay. The AO/EB staining and flow cytometry assay showed that PMBE induced S180 cell apoptosis. Cell cycle analysis revealed that the cells in the S phase were decreased by treatment with PMBE. In vivo, the treatment of 100, 200, and 300 mg/kg PMBE reduced the tumor weight and volume of S180-bearing NIH mice by 9%-67% and 13%-68%, respectively. Peripheral leukocyte count and lymphoproliferation were increased significantly after treatment with PMBE. Our results suggest that PMBE inhibits the tumor cell growth by inducing cell apoptosis and improving lymphoproliferation.

Chk2 and p53 are haploinsufficient with dependent and independent functions to eliminate cells after telomere loss.

The mechanisms that cells use to monitor telomere integrity, and the array of responses that may be induced, are not fully defined. To date there have been no studies in animals describing the ability of cells to survive and contribute to adult organs following telomere loss. We developed assays to monitor the ability of somatic cells to proliferate and differentiate after telomere loss. Here we show that p53 and Chk2 limit the growth and differentiation of cells that lose a telomere. Furthermore, our results show that two copies of the genes encoding p53 and Chk2 are required for the cell to mount a rapid wildtype response to a missing telomere. Finally, our results show that, while Chk2 functions by activating the p53-dependent apoptotic cascade, Chk2 also functions independently of p53 to limit survival. In spite of these mechanisms to eliminate cells that have lost a telomere, we find that such cells can make a substantial contribution to differentiated adult tissues.

Cancer pharmacogenomics and pharmacoepidemiology: setting a research agenda to accelerate translation.

Recent advances in genomic research have demonstrated a substantial role for genomic factors in predicting response to cancer therapies. Researchers in the fields of cancer pharmacogenomics and pharmacoepidemiology seek to understand why individuals respond differently to drug therapy, in terms of both adverse effects and treatment efficacy. To identify research priorities as well as the resources and infrastructure needed to advance these fields, the National Cancer Institute (NCI) sponsored a workshop titled "Cancer Pharmacogenomics: Setting a Research Agenda to Accelerate Translation" on July 21, 2009, in Bethesda, MD. In this commentary, we summarize and discuss five science-based recommendations and four infrastructure-based recommendations that were identified as a result of discussions held during this workshop. Key recommendations include 1) supporting the routine collection of germline and tumor biospecimens in NCI-sponsored clinical trials and in some observational and population-based studies; 2) incorporating pharmacogenomic markers into clinical trials; 3) addressing the ethical, legal, social, and biospecimen- and data-sharing implications of pharmacogenomic and pharmacoepidemiologic research; and 4) establishing partnerships across NCI, with other federal agencies, and with industry. Together, these recommendations will facilitate the discovery and validation of clinical, sociodemographic, lifestyle, and genomic markers related to cancer treatment response and adverse events, and they will improve both the speed and efficiency by which new pharmacogenomic and pharmacoepidemiologic information is translated into clinical practice.

Pinus massoniana bark extract selectively induces apoptosis in human hepatoma cells, possibly through caspase-dependent pathways.

Pinus massoniana bark extract (PMBE) is a mixture of flavonoids, whose antioxidant and apoptosis-inducing properties have been confirmed in vitro. In this study, the apoptotic effect and mechanism of PMBE in HepG2 human hepatoma cells were evaluated. PMBE exerted dose- and time-dependent cell growth inhibition on HepG2 cells, and selectively induced apoptosis without impact on normal liver L-02 cells. Apoptosis induced by PMBE in HepG2 cells was also confirmed by annexin-V/PI staining, transmission electron microscopy and sub-G1 phase accumulation. Moreover, PMBE also slightly blocked the cell cycle in the G2/M and S phases in HepG2 cells. The investigation of the mechanism by which PMBE induced apoptosis in HepG2 cells indicated that activation of extrinsic and intrinsic caspase, inhibition of NF-kappaB activation and decrease of the antiapoptotic protein Bcl-2 and the intact Bid protein were involved. Furthermore, the antitumor activity of PBME was demonstrated in vivo by a 42.88-69.94% reduction rate of tumor weight in H22 tumor-implanted mice. Taken together, these data indicate that PMBE selectively induces apoptosis in HepG2 cells through caspase-dependent pathways, and inhibits tumor growth in vivo, making it a potential candidate for anticancer therapeutics.

An efficient and aseptic preparation of "sodium fluoride ((18)F) injection" in a GMP compliant facility.

INTRODUCTION: "Sodium fluoride ((18)F) injection" is an isotonic NaCl solution containing [(18)F]NaF to be used as bone imaging agent. Although its NDA was approved by the US FDA in 1972, it has not been commercially available since 1975 due to mostly the popularity of (99m)Tc-MDP. Recently, advances in PET/CT technology and the often interrupted (99m)Tc supply have led to the renewed interest in the use of [(18)F]NaF to detect bone metastases in cancer patients. This report introduces an efficient, low-cost and aseptic preparation of "Sodium fluoride ((18)F) injection" for PET scan. METHOD: (18)F-Fluoride in target water from cyclotron was adsorbed onto four different forms of anion-exchange resins then desorbed by isotonic NaCl solution into the product vial. One of the resins that yielded the product at the suitable pH was used for the aseptic preparation. The components for this setup, including stopcocks, extension tubes, etc., were all single-use, individually packed and sterile. The process was done in a lead-line isolator maintained in grade A (PIC/S) aseptic condition. The quality of the obtained "Sodium fluoride ((18)F) injection" was analyzed according to its monograph in the European Pharmacopoeia (EP). RESULTS: The resin in the chloride form yielded the product of pH 6.7 and was chosen for the subsequent preparation. The radiochemical yield was quantitative. The product met all criteria specified in EP, including biological, physical and chemical specifications. CONCLUSIONS: This method is an efficient, space-saving and extremely low-cost operation that easily performed in an aseptic environment meeting GMP standard. The quality of the "Sodium fluoride ((18)F) injection" so yielded meets EP specifications. This setup provides hospital with facility meeting GMP standard a cost effective and efficient method for "Sodium fluoride ((18)F) injection" production without the need for the expensive automatic module and extra QC instrument.