Investigating the Relevance of Cyclic Adenosine Monophosphate Response Element-Binding Protein to the Wound Healing Process: An In Vivo Study Using Photobiomodulation Treatment.

Monitoring inflammatory cytokines is crucial for assessing healing process and photobiomodulation (PBM) enhances wound healing. Meanwhile, cAMP response element-binding protein (CREB) is a regulator of cellular metabolism and proliferation. This study explored potential links between inflammatory cytokines and the activity of CREB in PBM-treated wounds. A total of 48 seven-week-old male SD rats were divided into four groups (wound location, skin or oral; treatment method, natural healing or PBM treatment). Wounds with a 6 mm diameter round shape were treated five times with an 808 nm laser every other day (total 60 J). The wound area was measured with a caliper and calculated using the elliptical formula. Histological analysis assessed the epidermal regeneration and collagen expression of skin and oral tissue with H&E and Masson's trichrome staining. Pro-inflammatory (TNF-α) and anti-inflammatory (TGF-ß) cytokines were quantified by RT-PCR. The ratio of phosphorylated CREB (p-CREB) to unphosphorylated CREB was identified through Western blot. PBM treatment significantly reduced the size of the wounds on day 3 and day 7, particularly in the skin wound group (p < 0.05 on day 3, p < 0.001 on day 7). The density of collagen expression was significantly higher in the PBM treatment group (in skin wound, p < 0.05 on day 3, p < 0.001 on day 7, and p < 0.05 on day 14; in oral wound, p < 0.01 on day 7). The TGF-ß/TNF-α ratio and the p-CREB/CREB ratio showed a parallel trend during wound healing. Our findings suggested that the CREB has potential as a meaningful marker to track the wound healing process.

The causal relationship of colorectal cancer on schizophrenia: A Mendelian randomization study.

Comorbidities associated with psychiatric disorders often occur in patients with cancer. A causal effect of schizophrenia on cancer was observed using Mendelian randomization (MR) analysis. However, the causal effect of colorectal cancer on schizophrenia has not been studied using MR analysis. Therefore, we performed MR analysis to investigate the causal effects of colorectal cancer on schizophrenia. We performed "two-sample summary-data Mendelian randomization" using publicly available genome-wide association studies data to investigate the causal relationship between colorectal cancer (as exposure) and schizophrenia (as outcome). The inverse variance weighted method was used to calculate causal estimates. In 2 TSMR analyses, we reported that the odds ratios for schizophrenia per log odds increase in colorectal cancer risk were 6.48 (95% confidential interval [CI] of OR 1.75-24.03; P = .005) and 9.62 × 106 (95% CI of OR 1.13-8.22 × 1013; P = .048). Pleiotropic tests and sensitivity analysis demonstrated minimal horizontal pleiotropy and robustness of the causal relationship. We provide evidence for a causal relationship between the incidence of colorectal cancer and the development of schizophrenia through TSMR analysis.

Urban dust particles disrupt mitotic progression by dysregulating Aurora kinase B-related functions.

Particulate matter (PM), a major component of outdoor air pollution, damages DNA and increases the risk of cancer. Although the harmful effects of PM at the genomic level are known, the detailed mechanism by which PM affects chromosomal stability remains unclear. In this study, we investigated the novel effects of PM on mitotic progression and identified the underlying mechanisms. Gene set enrichment analysis of lung cancer patients residing in countries with high PM concentrations revealed the downregulation of genes associated with mitosis and mitotic structures. We also showed that exposure of lung cancer cells in vitro to urban dust particles (UDPs) inhibits cell proliferation through a prolonged M phase. The mitotic spindles in UDP-treated cells were hyperstabilized, and the number of centrioles increased. The rate of ingression of the cleavage furrow and actin clearance from the polar cortex was reduced significantly. The defects in mitotic progression were attributed to inactivation of Aurora B at kinetochore during early mitosis, and spindle midzone and midbody during late mitosis. While previous studies demonstrated possible links between PM and mitosis, they did not specifically identify the dysregulation of spatiotemporal dynamics of mitotic proteins and structures (e.g., microtubules, centrosomes, cleavage furrow, and equatorial and polar cortex), which results in the accumulation of chromosomal instability, ultimately contributing to carcinogenicity. The data highlight the novel scientific problem of PM-induced mitotic disruption. Additionally, we introduce a practical visual method for assessing the genotoxic outcomes of airborne pollutants, which has implications for future environmental and public health research.

Mild exposure to fine particulate matter promotes angiogenesis in non-small cell lung carcinoma.

Fine particulate matter (PM2.5) is associated with public health problems worldwide. Especially, PM2.5 induces epigenetic and microenvironmental changes in lung cancer. Angiogenesis is important for the development and growth of cancer and is mediated by angiogenic factors, including vascular endothelial growth factor. However, the effects of mild PM2.5 exposure on angiogenesis in lung cancer remain unclear. In this study, we examined angiogenic effects using relatively lower concentrations of PM2.5 than in other studies and found that PM2.5 increased angiogenic activities in both endothelial cells and non-small cell lung carcinoma cells. PM2.5 also promoted the growth and angiogenesis of lung cancer via the induction of hypoxia-inducible factor-1α (HIF-1α) in a xenograft mouse tumor model. Angiogenic factors, including vascular endothelial growth factor (VEGF), were highly expressed in lung cancer patients in countries with high PM2.5 levels in the atmosphere, and high expression of VEGF in lung cancer patients lowered the survival rate. Collectively, these results provide new insight into the mechanisms by which mild exposure to PM2.5 is involved in HIF-1α-mediated angiogenesis in lung cancer patients.

Association between the participation of the plastic surgery department and qualitative prognoses in severe trauma patients: A retrospective observational study.

Catastrophic incidents would necessitate the intervention of multiple specializations with plastic surgery (PS) as an indispensable area of expertise. In view of PS, prognostic assessment of trauma patients should be focused on the qualitative value rather than mortality because plastic surgeons rarely handled patients' vital signs in actual. Thus, we explored the association between the involvement of the PS department and qualitative prognoses for severe trauma patients. From November 2014 to December 2019, we enrolled total 529 trauma patients with an injury severity score (ISS) over 15 points. We set the prognostic factors that the rate of admission in intensive care unit (ICU), total or ICU duration of hospitalization, post-discharge progress and disability diagnosis which were regarded as qualitative prognoses. The analysis was performed with logistic regression analysis or regression analysis adjusted for age, sex, past medical history, cause of trauma, and frequency of operation. Among total of 529 patients, 290 patients in PS group and 239 patients in non-PS group were analyzed. In both groups, the under-65-year ages and male patients were significantly predominant. The rate of going home showed 2.082 times higher in PS group than non-PS group after adjusting for covariates, while there was no significant difference in diagnosis of disability. Meanwhile, overall prognoses were highly correlated with either higher ISS or lower Glasgow Coma Scale (GCS). In conclusion, higher severity generally affected to the severe trauma patient's prognoses, and the PS treatment only contributes to discharge disposition to home.

Pharmacological Activities for Morus alba L., Focusing on the Immunostimulatory Property from the Fruit Aqueous Extract.

Depending on the extraction method, numerous compounds that have specific pharmacological effects can be obtained from M. alba L. There is a growing scientific interest in health problems related to aging. Efforts to develop safe immune-enhancing pharmaceuticals are increasing. This review aims to summarize and critically discuss the immunity enhancement effects and pharmaceutical efficacy of M. alba L. extracts. The scientific database search was conducted using Google Scholar, Web of Science, and PubMed until May 2021. Additional articles were identified and obtained from references in the retrieved articles. Ethanol or methanol extraction of various parts of M. alba L. identified a large amount of phenols and flavonoids, which are effective for immunosuppression, antioxidants, and cardiovascular diseases, and are antibacterial, and anticancer. Water extraction of M. alba L. enhanced the innate immune response based on immune cell activation. A polysaccharide and an alkaloid related to increased macrophage activity were isolated from M. alba L. fruit extracts. M. alba L. fruit water extracts primarily induced the production of pro-inflammatory substances, in model organisms, via TLR4 in immune cells. Water extracts have been shown to be effective in pathogen defense and tumor suppression by enhancing macrophage activity. Based on our literature review on the bioactivity of M. alba L. fruit extracts, particularly in relation to their immunity enhancement activity, we anticipate that M. alba-derived pharmaceuticals will have excellent potential in future medical research.

The Improvement of Skin Whitening of Phenylethyl Resorcinol by Nanostructured Lipid Carriers.

Phenylethyl resorcinol (4-(1-phenylethyl)1,3-benzenediol) (PR) is a new whitening agent that has been found to have the ability to inhibit tyrosinase activity. However, the application of PR is limited by photo instability and poor solubility. PR-loaded nanostructured lipid carriers (PR-NLCs) were prepared by the hot-melted ultrasonic method. Glycerol monostearate and olive oil were selected as the solid lipid and liquid lipid for considering the solubility of PR in liquid lipid and partition coefficient of PR in solid lipid, respectively. The particle size and polydispersity index of PR-NLCs were 57.9 ± 1.3 nm and 0.24 ± 0.01, respectively. The encapsulation efficiency and loading capacity of PR-NLCs were 93.1 ± 4.2% and 8.5 ± 0.4%, respectively. The stability test demonstrated that the incorporation of PR into NLCs conferred excellent physicochemical stability and photo stability for at least three months at 4 °C in the dark and 25 °C under daylight. In vitro release of PR-NLCs revealed a sustained release pattern. Cellular tyrosinase assay showed that PR-NLCs could significantly inhibit tyrosinase activity in melanoma cells, suggesting that NLCs can be used as a biocompatible nanocarrier for the effective delivery of skin whitening agents.

In Vitro and in Vivo Effects of Nitrofurantoin on Experimental Toxoplasmosis.

Toxoplasma gondii is an important opportunistic pathogen that causes toxoplasmosis, which has very few therapeutic treatment options. The most effective therapy is a combination of pyrimethamine and sulfadiazine; however, their utility is limited because of drug toxicity and serious side effects. For these reasons, new drugs with lower toxicity are urgently needed. In this study, the compound, (Z)-1-[(5-nitrofuran-2-yl)methyleneamino]-imidazolidine-2,4-dione (nitrofurantoin), showed anti-T. gondii effects in vitro and in vivo. In HeLa cells, the selectivity of nitrofurantoin was 2.3, which was greater than that of pyrimethamine (0.9). In T. gondii-infected female ICR mice, the inhibition rate of T. gondii growth in the peritoneal cavity was 44.7% compared to the negative control group after 4-day treatment with 100 mg/kg of nitrofurantoin. In addition, hematology indicators showed that T. gondii infection-induced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, biochemical parameters involved in liver injury, were reduced by nitrofurantoin significantly. Moreover, nitrofurantoin exerted significant effects on the index of antioxidant status, i.e., malondialdehyde (MDA) and glutathione (GSH). The nitrofurantoin-treated group inhibited the T. gondii-induced MDA levels while alleviating the decrease in GSH levels. Thus, nitrofurantoin is a potential anti-T. gondii candidate for clinical application.

Melanogenesis inhibitory effect of aerial part of Pueraria thunbergiana in vitro and in vivo.

Melanin is major factor that determines skin color as well as one of the defense systems that prevent the UV-induced damage. In case of abnormal concentration of melanin, skin diseases or problems occur such as albinism, leukoplakia, melasma, freckles, moles, and lentigo. With the lifespan of humans has been extended, importance of 'life quality' has been increased. White and clean skin is very important part of the satisfaction of appearance, especially for Asia women. The aim of this study was to find an anti-melanogenesis activity for which the aerial part of Pueraria thunbergiana can be utilized based on the increase in demands for cosmetics, particularly natural products. We demonstrated anti-pigmentation effects of aerial part of P. thunbergiana by measuring melanin content and through staining in the B16F10 melanoma cell line. The aerial part of P. thunbergiana decreased tyrosinase activity significantly in B16F10 cell cultures, while there is no direct effect on enzyme in cell-free conditions. To define the mechanisms, real-time PCR, western blot, glucosidase activity and antioxidant activity assay were implemented. As results, we demonstrated that aerial part of P. thunbergiana has anti-melanogenesis activity via two mechanisms. One is downgrading microphthalmia-associated transcription factor by activating Akt/GSK-3ß. Consequently, transcription of tyrosinase and tyrosinase-related protein 1 is decreased. Another is interrupting maturation of tyrosinase through inhibiting α-glucosidase. Furthermore, aerial part of P. thunbergiana showed great efficacy on pigmentation in vivo. These results suggest that aerial part of P. thunbergiana can be used as an anti-melanogenic agent.

6-trifluoromethyl-2-thiouracil possesses anti-Toxoplasma gondii effect in vitro and in vivo with low hepatotoxicity.

Since pyrimethamine, the general therapeutic drug for toxoplasmosis, presents several adverse side effects, the need to develop and evaluate new drugs for the condition is critical. In this study, anti-Toxoplasma gondii activities of 3-[{2-((E)-furan-2-ylmethylene)hydrazinyl}methylene]-1,3-dihydroindol-2-one (ATT-5126) and 6-trifluoromethyl-2-thiouracil (KH-0562) were evaluated in vitro using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and in vivo by measuring amount of the tachyzoites in mice ascites. Biochemical parameters such as lipid peroxidation (LPO), glutathione (GSH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were also evaluated in livers of mice at 4 days post-infection. As a result, the ATT-5126 and KH-0562 showed anti-T. gondii activity in vitro. Treatment of ATT-5126 or KH-0562 decreased the amount of tachyzoites in T. gondii infected ICR mice. The relative weight of liver and spleen increased by T. gondii infection were decreased by treatment of ATT-5126 or KH-0562. The levels of LPO, ALT and AST, which are biochemical parameters involved in liver injury, were also significantly recovered by treatment of ATT-5126 or KH-0562 (p<0.05). In particular, the recovered levels by KH-0562 were similar to those of pyrimethamine-treated group (p<0.05). However, the level of GSH, which is an antioxidant indicator, showed insignificant statistics. The results suggest that KH-0562 show anti-T. gondii activities in vitro and in vivo with low hepatotoxicity. Therefore, KH-0562 may be a useful candidate for treating T. gondii infection.

Protective effects of the ethanolic extract of Melia toosendan fruit against colon cancer.

Colorectal cancer is one of the leading causes of death in the world. Plant-derived products have proven to be valuable sources for discovery and development of unique anticancer drugs. In this study, the inhibitory effects of ethanolic extract of Melia toosendan fruit (EMTF), a traditional medicine in the Chinese Pharmacopeia were evaluated in vitro and in vivo against colon cancer. Human colon cancer cells SW480 and murine colorectal adenocarcinoma cells CT26 were used to investigate cell proliferation. The results showed that EMTF inhibited cell proliferation of SW480 and CT26 by promoting apoptosis as indicated by nuclear chromatin condensation and DNA fragmentation. Through increasing mitochondrial membrane permeability and cytochrome c release from mitochondria, EMTF induced caspase-9 activity which further activated caspase-3 and poly(ADP-ribose) polymerase cleavage, leading the tumor cells to apoptosis. The in vivo results confirmed reduction of tumor volume and apoptotic effects and the side effects were not induced by EMTF. Therefore, EMTF may be an effective chemotherapeutic agent for colon cancer treatment.

Brevicompanine E reduces lipopolysaccharide-induced production of proinflammatory cytokines and enzymes in microglia by inhibiting activation of activator protein-1 and nuclear factor-kappaB.

Excessive release of proinflammatory cytokines by activated microglia can cause neurotoxicity in neurodegenerative diseases. We found that Brevicompanine E (BE), isolated from a deep ocean sediment derived fungus Penicillium sp., inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) production in microglia. Moreover, electrophoretic mobility shift assay (EMSA) demonstrated that BE attenuated nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) DNA binding activity in LPS-induced microglia. Consistent with this finding, BE inhibited LPS-induced IkappaBalpha degradation, NF-kappaB nuclear translocation, and also Akt, c-Jun NH2-terminal kinase (JNK) phosphorylation. Thus, BE may be potentially useful for modulating neuroinflammation.

Asiatic acid induces colon cancer cell growth inhibition and apoptosis through mitochondrial death cascade.

Cancer is one of the leading causes of death in the world. The triterpenoid compound asiatic acid derived from the tropical medicinal plant Centella asiatica displays cytotoxic activity on fibroblast cells and several other kinds of cells. The present work studies asiatic acid-mediated growth inhibition of cancer cells and the underlying mechanism. Asiatic acid markedly inhibited cancer cell proliferation. Apoptosis of SW480 human colon cancer cells was induced by asiatic acid as shown by flow cytometry, DNA fragmentation and nuclear chromatin condensation experiments. Through increasing mitochondrial membrane permeability and cytochrome c release from mitochondria into cytosol, asiatic acid induced caspase-9 activity, which further activated caspase-3 and poly(ADP-ribose) polymerase cleavage resulting in irreversible apoptotic death in the tumor cells. Taken together, these results suggest that mitochondrial death apoptosis cascade plays very important roles in asiatic acid-induced cancer apoptosis.