Roles of oxidative stress/JNK/ERK signals in paraquat-triggered hepatic apoptosis.

Paraquat (PQ), a toxic and nonselective bipyridyl herbicide, is one of the most extensively used pesticides in agricultural countries. In addition to pneumotoxicity, the liver is an important target organ for PQ poisoning in humans. However, the mechanism of PQ in hepatotoxicity remains unclear. In this study, we found that exposure of rat hepatic H4IIE cells to PQ (0.1-2 mM) induced significant cytotoxicity and apoptosis, which was accompanied by mitochondria-dependent apoptotic signals, including loss of mitochondrial membrane potential (MMP), cytosolic cytochrome c release, and changes in the Bcl-2/Bax mRNA ratio. Moreover, PQ (0.5 mM) exposure markedly induced JNK and ERK1/2 activation, but not p38-MAPK. Blockade of JNK and ERK1/2 signaling by pretreatment with the specific pharmacological inhibitors SP600125 and PD98059, respectively, effectively prevented PQ-induced cytotoxicity, mitochondrial dysfunction, and apoptotic events. Additionally, PQ exposure stimulated significant oxidative stress-related signals, including reactive oxygen species (ROS) generation and intracellular glutathione (GSH) depletion, which could be reversed by the antioxidant N-Acetylcysteine (NAC). Buffering the oxidative stress response with NAC also effectively abrogated PQ-induced hepatotoxicity, MMP loss, apoptosis, and phosphorylation of JNK and ERK1/2 protein, however, the JNK or ERK inhibitors did not suppress ROS generation in PQ-treated cells. Collectively, these results demonstrate that PQ exposure induces hepatic cell toxicity and death via an oxidative stress-dependent JNK/ERK activation-mediated downstream mitochondria-regulated apoptotic pathway.

Isolation and characterization of bacteriophages with activities against multi-drug-resistant Acinetobacter nosocomialis causing bloodstream infection in vivo.

BACKGROUND: Acinetobacter nosocomialis (A. nosocomialis) is a glucose non-fermentative, gram-negative bacillus that belongs to the Acinetobacter calcoaceticus-baumannii complex. In recent years, studies have found an increased clinical prevalence of A. nosocomialis. However, given the increasing trend of antibiotic resistance, developing new antibacterial agents is vital. Currently, research regarding bacteriophage therapy against A. nosocomialis is only limited. METHODS: Two A. nosocomialis bacteriophages, TCUAN1 and TCUAN2, were isolated from sewage. Experiments such as transmission electron microscopy (TEM), host-range analysis, and sequencing were performed to determine their biological and genomic characteristics. TCUAN2 were further subjected to in vivo experiments and their derived-endolysin were cloned and tested against their bacteria host. RESULTS: Transmission electron microscopy revealed that TCUAN1 and TCUAN2 belong to Myoviridae and Podoviridae, respectively. Both phages show a broad host spectrum and rapid adsorption efficiency. Further biological analysis showed that TCUAN2 possesses a shorter latent period and larger burst size compared to TCUAN1. Because TCUAN2 showed a better antibacterial activity, it was injected into A. nosocomialis-infected mice which resulted in a significant decrease in bacterial load levels in the blood and increased the mice's survival. Finally, genomic analysis revealed that the complete nucleotide sequence of TCUAN1 is 49, 691 bps (containing 75 open reading frames) with a G + C content of 39.3%; whereas the complete nucleotide sequence of TCUAN2 is 41, 815 bps (containing 68 open reading frames) with a G + C content of 39.1%. The endolysin gene cloned and purified from TCUAN2 also showed antibacterial activity when used with a chelator EDTA.

Personalized Privacy Assistant: Identity Construction and Privacy in the Internet of Things.

Over time, the many different ways in which we collect and use data have become more complex as we communicate and interact with an ever-increasing variety of modern technologies. Although people often say they care about their privacy, they do not have a deep understanding of what devices around them are collecting their identity information, what identity information is being collected, and how that collected data will affect them. This research is dedicated to developing a personalized privacy assistant to help users regain control, understand their own identity management, and process and simplify the large amount of information from the Internet of Things (IoT). This research constructs an empirical study to obtain the comprehensive list of identity attributes that are being collected by IoT devices. We build a statistical model to simulate the identity theft and to help calculate the privacy risk score based on the identity attributes collected by IoT devices. We discuss how well each feature of our Personal Privacy Assistant (PPA) works and compare the PPA and related work to a list of fundamental features for privacy protection.

Recent developments in detection and therapeutic approaches for antibiotic-resistant bacterial infections.

Owing to the widespread emergence and proliferation of antibiotic-resistant bacteria, the therapeutic benefits of antibiotics have been reduced. In addition, the ongoing evolution of multidrug-resistant pathogens poses a challenge for the scientific community to develop sensitive analytical methods and innovative antimicrobial agents for the detection and treatment of drug-resistant bacterial infections. In this review, we have described the antibiotic resistance mechanisms that occur in bacteria and summarized the recent developments in detection strategies for monitoring drug resistance using different diagnostic methods in three aspects, including electrostatic attraction, chemical reaction, and probe-free analysis. Additionally, to understand the effective inhibition of drug-resistant bacterial growth by recent nano-antibiotics, the underlying antimicrobial mechanisms and efficacy of biogenic silver nanoparticles and antimicrobial peptides, which have shown promise, and the rationale, design, and potential improvements to these methods are also highlighted in this review. Finally, the primary challenges and future trends in the rational design of facile sensing platforms and novel antibacterial agents against superbugs are discussed.

Salmonella typhimurium exacerbates injuries but resolves fibrosis in liver and spleen during Schistosoma mansoni infection.

BACKGROUND: In most developing or undeveloped countries, patients are often co-infected with multiple pathogens rather than a single pathogen. While different pathogens have their impact on morbidity and mortality, co-infection of more than one pathogen usually made the disease outcome different. Many studies reported the co-infection of Schistosoma with Salmonella in pandemic areas. However, the link or the underlying mechanism in the pathogenesis caused by Schistosoma-Salmonella co-infection is still unknown. METHODS: In this study, Salmonella typhimurium (S. typhimurium) was challenged to Schistosoma mansoni (S. mansoni)-infected mice. Further experiments such as bacterial culture, histopathological examination, western blotting, and flow cytometry were performed to evaluate the outcomes of the infection. Cytokine responses of the mice were also determined by ELISA and real-time quantitative PCR. RESULTS: Our results demonstrated that co-infected mice resulted in higher bacterial excretion in the acute phase but higher bacterial colonization in the chronic phase. Lesser egg burden was also observed during chronic schistosomiasis. Infection with S. typhimurium during schistosomiasis induces activation of the inflammasome and apoptosis, thereby leading to more drastic tissue damage. Interestingly, co-infected mice showed a lower fibrotic response in the liver and spleen. Further, co-infection alters the immunological functioning of the mice, possibly the reason for the observed pathological outcomes. CONCLUSION: Collectively, our findings here demonstrated that S. mansoni-infected mice challenged with S. typhimurium altered their immunological responses, thereby leading to different pathological outcomes.

Idiopathic Mesenteric Phlebosclerosis: A Single-Institute Experience in Taiwan.

BACKGROUND: Idiopathic mesenteric phlebosclerosis is a rare condition with unclear pathogenesis. This study aimed to investigate the clinical features, diagnostic modalities, treatments, and outcomes of idiopathic mesenteric phlebosclerosis patients in Taiwan. METHODS: Idiopathic mesenteric phlebosclerosis patients diagnosed by the typical characteristic of tree-like mesenteric venous calcifications on plain abdominal radiography or computed tomography between January 1992 and July 2021 were retrospectively analyzed. RESULTS: Totally, 36 idiopathic mesenteric phlebosclerosis patients were enrolled (50% females; mean age, 61.6 years). Among the included patients, 26 (72.2%) and 10 (27.7%) were symptomatic and asymptomatic, respectively. Abdominal pain (61.1%) accounted for the majority of all symptoms, followed by fever, diarrhea, and bloody stools. Our results showed that 83.3% of patients had at least 1 risk factor, whereas 16.6% of patients had none. Moreover, among the included patients, 36.1%, 44.4%, 50.0%, 38.8%, and 8.3% had cardiovascular disease, chronic renal disease, cancer, chronic liver disease, and diabetes mellitus, respectively. Our findings showed 94.4% of patients were diagnosed via abdominal computed tomography and plain abdominal radiography, whereas 5.6% of patients were diagnosed via plain abdominal radiography. The ascending colon was the most commonly involved site (100%). Our findings showed that 91.6% of patients experienced good recovery after conservative treatment, except for the 3 who died of sepsis and respiratory failure. By contrast, 8.3% of idiopathic mesenteric phlebosclerosis patients underwent colectomy. The average follow-up duration was 62.5 months. CONCLUSIONS: Idiopathic mesenteric phlebosclerosis remains a rare disease in Taiwan. Plain abdominal radiography and computed tomography can be utilized for establishing a definite diagnosis. Conservative treatment is usually adequate for most patients, with surgical treatment only indicated for severe cases.

Chlorpyrifos induces neuronal cell death via both oxidative stress and Akt activation downstream-regulated CHOP-triggered apoptotic pathways.

Chlorpyrifos (CPF) is one of the most abundant and widely used organophosphate pesticides for agricultural, industrial, and household purposes in the world. Epidemiological studies have reported that CPF can induce neurotoxic impairments in mammalian, which is linked to an important risk factor for development of neurodegenerative diseases (NDs). However, limited information is available on CPF-induced neurotoxicity, with the underlying exact mechanism remains unclear. In this study, CPF exposure (10-400 µM) significantly reduced Neuro-2a cell viability and induced apoptotic events, including the increase in caspase-3 activity, apoptotic cell population, and cleavage of caspase-3/-7 and PARP. Exposure of Neuro-2a cells to CPF also triggered CHOP activation. Transfection with CHOP-specific siRNA markedly suppressed the expression of CHOP, and attenuated cytotoxicity and apoptotic events in CPF-exposed Neuro-2a cells. Furthermore, CPF exposure obviously evoked the phosphorylation of Akt as well as ROS generation in a time-dependent manner. Pretreatment with LY294002 (an Akt inhibitor) effectively attenuated the CPF-induced Akt phosphorylation, CHOP activation, and apoptotic events, but not that ROS production. Of note, buffering the ROS generation with antioxidant N-acetylcysteine effectively prevented the CPF-induced ROS generation, CHOP activation, and apoptotic events, but not that the Akt phosphorylation. Collectively, these findings indicate that CPF exposure exerts neuronal cytotoxicity via the independent pathways of ROS generation and Akt activation downstream-regulated CHOP-triggered apoptosis, ultimately leading to neuronal cell death.

Evaluating Antioxidant Performance, Biosafety, and Antimicrobial Efficacy of Houttuynia cordata Extract and Microwave-Assisted Synthesis of Biogenic Silver Nano-Antibiotics.

From the traditional Chinese medicine point of view, although Houttuynia cordata extract (HCE) possesses an incredible amount of phytonutrients and exhibits antioxidant activities, excessive doses of HCE can cause danger to organisms and lead to death. In this study, we first examine HCE's overall phenolic and flavonoid content, antioxidant efficacy, and antibacterial activity. Results show that HCE is suitable as a bio-reducing agent for the microwave-assisted synthesis of silver nanoparticles (HCE-AgNPs) with enhanced antioxidant and antimicrobial performance. Under an optimized microwave condition (i.e., 100 °C for 10 min), the HCE-stabilized AgNPs were confirmed with a UV-visible peak at 430 nm and 19.7 ± 4.2 nm in size. Physicochemical properties of HCE-AgNPs were extensively characterized by zeta-potential, FT-IR, XRD, and XPS measurements. Compared to the HC extract counterpart, HCE-AgNPs display superior antioxidant activity, higher DPPH scavenging efficiency, and enhanced broad-spectrum bactericidal activity to inhibit the growth of all tested bacterial strains at doses of 2 µg/mL. Biosafety evaluation indicated that HCE-AgNPs are noncytotoxic on human red blood cells. These data show that the microwave synthesis of AgNPs exhibits a great antioxidant ability, superior antibacterial activity, and a trivial hemolytic effect, providing another bactericidal therapy strategy to address the increasing healthcare-associated infections.

Involvement of AMPKα and MAPK-ERK/-JNK Signals in Docetaxel-Induced Human Tongue Squamous Cell Carcinoma Cell Apoptosis.

Cancers of the oral cavity can develop in the anatomic area extending from the lip, gum, tongue, mouth, and to the palate. Histologically, about 85-90% of oral cavity cancers are of the type squamous cells carcinomas (SCCs). The incidence of oral tongue SCC is higher in the tongue than any other anatomic area of the oral cavity. Here, we investigated the therapeutic effects and molecular mechanisms of docetaxel, which is a paclitaxel antitumor agent, on the cell growth of a human tongue SCC-derived SAS cell line. The results showed that docetaxel (10-300 nM) induced cytotoxicity and caspase-3 activity in SAS cells. Moreover, docetaxel (100 nM) promoted the expression of apoptosis-related signaling molecules, including the cleavages of caspase-3, caspase-7, and poly (ADP-ribose) polymerase (PARP). In mitochondria, docetaxel (100 nM) decreased the mitochondrial membrane potential (MMP) and Bcl-2 mRNA and protein expression and increased cytosolic cytochrome c protein expression and Bax mRNA and protein expression. In terms of mitogen-activated protein kinase (MAPK) and adenosine monophosphate-activated protein kinase (AMPK) signaling, docetaxel increased the expression of phosphorylated (p)-extracellular signal-regulated kinase (ERK), p-c-Jun N-terminal kinase (JNK), and p-AMPKα protein expression but not p-p38 protein expression. Moreover, the increase in caspase-3/-7 activity and Bax protein expression and decreased Bcl-2 protein expression and MMP depolarization observed in docetaxel-treated SAS cells could be reversed by treatment with either SP600125 (a JNK inhibitor), PD98059 (an MEK1/2 (mitogen-activated protein kinase kinase 1/2) inhibitor), or compound c (an AMPK inhibitor). The docetaxel-induced increases in p-JNK, p-ERK, and p-AMPKα protein expression could also be reversed by treatment with either SP600125, PD98059, or compound c. These results indicate that docetaxel induces human tongue SCC cell apoptosis via interdependent MAPK-JNK, MAPK-ERK1/2, and AMPKα signaling pathways. Our results show that docetaxel could possibly exert a potent pharmacological effect on human oral tongue SCC cell growth.

Biological and genomic characterization of two newly isolated Elizabethkingia anophelis bacteriophages.

BACKGROUND: Elizabethkingia anophelis is an opportunistic pathogen that infects newborns and immunocompromised patients. Because the infection is associated with high mortality as a result of its intrinsic resistance to antibiotics, alternative treatment methods are needed. Our previous study successfully isolated the world's first E. anophelis phage, TCUEAP1, which showed beneficial protection to E. anophelis-infected mice. More new bacteriophages are needed in order to provide sufficient choices to combat E. anophelis infections. METHODS: In the current study, two new phages infecting E. anophelis were isolated from wastewater and were designated as TCUEAP2 and TCUEAP3. Further experiments, namely, transmission electron microscopy (TEM), infection assay, host-range analysis, and sequencing were performed to determine their biological and genomic characteristics. RESULTS: TEM analysis revealed that both TCUEAP2 and TCUEAP3 possess an icosahedral head with a non-contractile tail, and belong to the Siphoviridae family. Further experiments revealed that TCUEAP3 has a longer latent period and higher burst size compared to TCUEAP2. Host range analysis showed that both TCUEAP2 and TCUEAP3 have a narrow host range, infecting only their respective hosts. The genomic size of phage TCUEAP2 was 42,403 bps containing 61 predicted open reading frames (ORFs), whereas the genome size of TCUEAP3 was 37,073 bps containing 40 predicted ORFs. CONCLUSION: Due to the distinct biological characteristics of TCUEAP2 and TCUEAP3, they may be satisfactory for clinical uses such as preparation of phage cocktails or decontamination in clinical settings.

Norketamine, the Main Metabolite of Ketamine, Induces Mitochondria-Dependent and ER Stress-Triggered Apoptotic Death in Urothelial Cells via a Ca2+-Regulated ERK1/2-Activating Pathway.

Ketamine-associated cystitis is characterized by suburothelial inflammation and urothelial cell death. Norketamine (NK), the main metabolite of ketamine, is abundant in urine following ketamine exposure. NK has been speculated to exert toxic effects in urothelial cells, similarly to ketamine. However, the molecular mechanisms contributing to NK-induced urothelial cytotoxicity are almost unclear. Here, we aimed to investigate the toxic effects of NK and the potential mechanisms underlying NK-induced urothelial cell injury. In this study, NK exposure significantly reduced cell viability and induced apoptosis in human urinary bladder epithelial-derived RT4 cells that NK (0.01-0.5 mM) exhibited greater cytotoxicity than ketamine (0.1-3 mM). Signals of mitochondrial dysfunction, including mitochondrial membrane potential (MMP) loss and cytosolic cytochrome c release, were found to be involved in NK-induced cell apoptosis and death. NK exposure of cells also triggered the expression of endoplasmic reticulum (ER) stress-related proteins including GRP78, CHOP, XBP-1, ATF-4 and -6, caspase-12, PERK, eIF-2α, and IRE-1. Pretreatment with 4-phenylbutyric acid (an ER stress inhibitor) markedly prevented the expression of ER stress-related proteins and apoptotic events in NK-exposed cells. Additionally, NK exposure significantly activated JNK, ERK1/2, and p38 signaling and increased intracellular calcium concentrations ([Ca2+]i). Pretreatment of cells with both PD98059 (an ERK1/2 inhibitor) and BAPTA/AM (a cell-permeable Ca2+ chelator), but not SP600125 (a JNK inhibitor) and SB203580 (a p38 inhibitor), effectively suppressed NK-induced mitochondrial dysfunction, ER stress-related signals, and apoptotic events. The elevation of [Ca2+]i in NK-exposed cells could be obviously inhibited by BAPTA/AM, but not PD98059. Taken together, these findings suggest that NK exposure exerts urothelial cytotoxicity via a [Ca2+]i-regulated ERK1/2 activation, which is involved in downstream mediation of the mitochondria-dependent and ER stress-triggered apoptotic pathway, consequently resulting in urothelial cell death. Our findings suggest that regulating [Ca2+]i/ERK signaling pathways may be a promising strategy for treatment of NK-induced urothelial cystitis.

Methylmercury Induces Mitochondria- and Endoplasmic Reticulum Stress-Dependent Pancreatic ß-Cell Apoptosis via an Oxidative Stress-Mediated JNK Signaling Pathway.

Methylmercury (MeHg), a long-lasting organic pollutant, is known to induce cytotoxic effects in mammalian cells. Epidemiological studies have suggested that environmental exposure to MeHg is linked to the development of diabetes mellitus (DM). The exact molecular mechanism of MeHg-induced pancreatic ß-cell cytotoxicity is still unclear. Here, we found that MeHg (1-4 µM) significantly decreased insulin secretion and cell viability in pancreatic ß-cell-derived RIN-m5F cells. A concomitant elevation of mitochondrial-dependent apoptotic events was observed, including decreased mitochondrial membrane potential and increased proapoptotic (Bax, Bak, p53)/antiapoptotic (Bcl-2) mRNA ratio, cytochrome c release, annexin V-Cy3 binding, caspase-3 activity, and caspase-3/-7/-9 activation. Exposure of RIN-m5F cells to MeHg (2 µM) also induced protein expression of endoplasmic reticulum (ER) stress-related signaling molecules, including C/EBP homologous protein (CHOP), X-box binding protein (XBP-1), and caspase-12. Pretreatment with 4-phenylbutyric acid (4-PBA; an ER stress inhibitor) and specific siRNAs for CHOP and XBP-1 significantly inhibited their expression and caspase-3/-12 activation in MeHg-exposed RIN-mF cells. MeHg could also evoke c-Jun N-terminal kinase (JNK) activation and reactive oxygen species (ROS) generation. Antioxidant N-acetylcysteine (NAC; 1mM) or 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox; 100 µM) markedly prevented MeH-induced ROS generation and decreased cell viability in RIN-m5F cells. Furthermore, pretreatment of cells with SP600125 (JNK inhibitor; 10 µM) or NAC (1 mM) or transfection with JNK-specific siRNA obviously attenuated the MeHg-induced JNK phosphorylation, CHOP and XBP-1 protein expression, apoptotic events, and insulin secretion dysfunction. NAC significantly inhibited MeHg-activated JNK signaling, but SP600125 could not effectively reduce MeHg-induced ROS generation. Collectively, these findings demonstrate that the induction of ROS-activated JNK signaling is a crucial mechanism underlying MeHg-induced mitochondria- and ER stress-dependent apoptosis, ultimately leading to ß-cell death.

Meckel's diverticulum diagnosed by double-balloon enteroscopy: A single-center retrospective study in Taiwan.

BACKGROUND AND AIM: Meckel's diverticulum (MD) is a common congenital abnormality of the gastrointestinal (GI) tract. Although a few patients with MD present symptoms, preoperative diagnosis of MD is a clinical challenge because of its endoscopic inaccessibility. The aim of the present study was to investigate patients with MD diagnosed by double-balloon enteroscopy (DBE) in Taiwan. METHODS: We conducted a retrospective study in a tertiary referral center in middle Taiwan. The clinical characteristics, endoscopic features, histopathological findings, treatment methods, and outcomes of patients with MD diagnosed by DBE were analyzed. RESULTS: A total of 14 male patients with MD diagnosed by DBE were enrolled. The mean age of all patients was 32.3 years. GI bleeding (78.6%) accounted for the major indication of DBE, followed by abdominal pain and Crohn's disease follow-up. The mean distance between the ileocecal valve and MD was 68.9 cm. The average length of 12 patients with surgically resected MD was 5.2 cm. The diagnostic yields of the other modalities excepting DBE are as follows: capsule endoscopy, 50%; Meckel's scan, 11.1%; computed tomography, 16.7%; small bowel series, 0%; and angiography, 33.3%. MD presented as a large ostium in 13 patients (92.9%), a small ostium in 1 patient (7.1%), and bleeding signs in 10 patients (71.4%). Twelve patients (85.7%) underwent surgical treatment and 2 patients (14.3%) received conservative treatment. Heterotopic gastric tissue was identified in 4 patients (28.6%). CONCLUSION: The present study showed that DBE is a more powerful modality in detecting MD than the other conventional modalities in Taiwan.

Increased immunogenicity and protection of recombinant Sm14 antigens by heat-killed Cutibacterium acnes in BALB/c mice infected with Schistosoma mansoni.

After many years of the excessive use of praziquantel against Schistosoma mansoni (S. mansoni), it has already led to the development of drug resistance. While schistosomiasis is still affecting millions of people every year, vaccination may be one realistic alternative way to control the disease. Currently, S. mansoni 14-kDa fatty acid-binding protein (Sm14) has shown promising results as a vaccine antigen. Yet, the use of an adjuvant may be necessary to further increase the effectiveness of the vaccine. Herein, we investigated the potential of using heat-killed Cutibacterium acnes (C. acnes) as an adjuvant for recombinant Sm14 (rSm14). Immunization of mice with C. acnes-adjuvanted rSm14 showed increased humoral immune responses, compared with mice immunized with rSm14 alone. Additionally, C. acnes-adjuvanted rSm14 vaccination provided higher protection to mice against S. mansoni infection and liver injuries. These results suggest that C. acnes increases the immunogenicity of rSm14, which leads to better protection against S. mansoni infection. Therefore, heat-killed C. acnes may be a promising adjuvant to use with rSm14.

Antifibrotic and anthelminthic effect of casticin on Schistosoma mansoni-infected BALB/c mice.

BACKGROUND/PURPOSE: Schistosomiasis is an important tropical disease caused by Schistosoma. Although the pathogenesis of liver fibrosis has been intensively studied, the choice of effective treatment is still inadequate. In this study, we aimed to investigate the potential of using Casticin to treat Schistosoma mansoni-induced liver fibrosis. METHODS: BALB/c mice were divided into three groups - control, infection, and treatment group. The infection and treatment group were percutaneously infected with 100-120 cercariae. Mice from the treatment group were treated with 20 mg/kg/day Casticin for 14 consecutive days to investigate the potential protective effects of Casticin. Mice were sacrificed and were used for histological, RNA, protein, and parasite burden analysis. RESULTS: Our results showed that hepatic fibrosis was significantly attenuated, as indicated by histology and reduction of fibrotic markers such as collagen AI, transforming growth factor ß (TGF-ß), and α-smooth muscle actin (α-SMA). Furthermore, Casticin treatment significantly reduced worm burden. Anthelmintic effect of Casticin was also observed by scanning electron microscopy. CONCLUSION: Collectively, our study suggested that Casticin may be a beneficial candidate in treating S. mansoni infection.

Antimicrobial and Immunomodulatory Activity of Herb Extracts Used in Burn Wound Healing: "San Huang Powder".

"San Huang Powder," a nonsterile milled herb powder, is frequently used to treat burn wounds in traditional Chinese herbal medicine. However, treating a wound with a nonsterile dressing or reagent is not compatible with the current guidelines in modern medicine. Therefore, we investigated the bactericidal and anti-inflammatory activities of four herb extracts used in "San Huang Powder" in vitro. Meanwhile, an in vivo porcine model with superficial second-degree burns was used for the experiments since the size and skin composition of pigs are the closest to that of the human body. The minimal bactericidal concentration (MBC) of the herb extracts was determined. The in vitro assay indicated that Rhubarb and Phellodendron bark extracts decreased the levels of inflammatory cytokines, IL-8, and GM-CSF on LPS-induced HMEC-1 cells. In accordance with this result, the histopathological evaluation results showed that the efficacy of "San Huang Powder" containing both herb materials was much better than the group without Rhubarb. Our results not only provide a basis to understand why "San Huang Powder" has been used to clinically treat wounds without sterilization directly since ancient times but also show the advantages of using multiple herb materials simultaneously on wound sites to prevent infection during treatment. Rhubarb is the recommended ingredient involved in the preparation of "San Huang Powder" to ensure the healing efficacy of burn wounds.

Systematic Evaluation of Antioxidant Efficiency and Antibacterial Mechanism of Bitter Gourd Extract Stabilized Silver Nanoparticles.

In this study, we accentuate the facile and green synthesis of ecologically viable silver nanoparticles (AgNPs) using aqueous (A-BGE) and ethanolic (E-BGE) dried bitter gourd (Momordica charantia) fruit extract as reducing and capping agents. Although AgNPs synthesized using BGEs have been reported earlier in fundamental antimicrobial studies, the possible antioxidant activity, antibacterial efficacy against superbugs, and a potential antimicrobial mechanism are still lacking. The characterization of as-prepared AgNPs was studied through UV-vis, TEM, Zeta-potential, FT-IR, XRD, and XPS analysis. The antioxidant ability of BG-AgNPs was extensively evaluated through DPPH and FRAP assays, which showed that A-BG-AgNPs possessed higher scavenging ability and superior reducing power due to the high phenolic content present in the BG extract. Furthermore, A-BG-AgNPs were highly stable in various physiological media and displayed excellent antibacterial activity against drug-resistant bacterial strains (i.e., MIC value of 4 µg/mL). The generation of reactive oxygen species evidenced that the possible antimicrobial mechanism was induced by BG-AgNPs, resulting in bacterial cell damage. Within the minimal hemolysis, the BG-mediated AgNPs possessed synergistic antioxidant and antibacterial agents and open another avenue for the inhibition of the growth of pathogens.

Comparison of 10 noninvasive models for predicting overall survival in patients with intermediate-stage hepatocellular carcinoma.

ABSTRACT: Intermediate-stage hepatocellular carcinoma (HCC) is heterogeneous in terms of tumor size, number, and effects on liver function. Various noninvasive models have been proposed to assess functional hepatic reserve or fibrosis severity in patients with HCC. This study assessed the feasibility of 10 noninvasive models and compared their prognostic ability for patients with intermediate-stage HCC.This study retrospectively enrolled 493 patients with intermediate-stage HCC who received treatment at China Medical University Hospital from January 2012 to November 2018. Demographic data, clinical features, and factors associated with overall survival (OS) were recorded at baseline. Receiver-operating characteristic curve analysis and the DeLong method were respectively employed to evaluate and compare the models' OS prediction performance.Of the 493 patients, 373 (75.7%) were male, and 275 (55.8%) had liver cirrhosis (LC). The median age was 64 years (interquartile range: 55-72). Most patients had tumor volume ≤50% (n = 424, 86.0%), and the maximum tumor size was 6.0 (4.0-8.5) cm. The median α-fetoprotein was 36.25 (6.13-552.91) ng/mL. The patients underwent transarterial chemoembolization (TACE, n = 349) or surgery (n = 144). The median follow-up period was 26.07 (9.77-48.27) months. Across the 10 models, the albumin-bilirubin (ALBI) score had the highest area under the receiver operating characteristic curve (AUROC) (0.644, 95% confidence interval: 0.595-0.693) in all patients. In subgroup analyses, the Lok index, platelet-albumin-bilirubin score, ALBI score, and Lok index had the highest AUROC values in patients without cirrhosis, with cirrhosis, undergoing TACE, and undergoing surgery, respectively. Multivariate Cox regression analysis revealed that independent predictors of longer OS were ALBI grade 1 in all patients, patients with LC, and patients undergoing TACE and Lok index grade 1 in patients without LC and patients undergoing surgery.Among the 10 noninvasive models, ALBI score exhibited the highest diagnostic value in predicting OS for all patients, patients with cirrhosis, and those undergoing TACE, and Lok index grade exhibited the highest diagnostic value in predicting OS in patients without cirrhosis and those undergoing surgery.

Selective Capture and Identification of Methicillin-Resistant Staphylococcus aureus by Combining Aptamer-Modified Magnetic Nanoparticles and Mass Spectrometry.

A nucleic acid aptamer that specifically recognizes methicillin-resistant Staphylococcus aureus (MRSA) has been immobilized on magnetic nanoparticles to capture the target bacteria prior to mass spectrometry analysis. After the MRSA species were captured, they were further eluted from the nanoparticles and identified using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). The combination of aptamer-based capture/enrichment and MS analysis of microorganisms took advantage of the selectivity of both techniques and should enhance the accuracy of MRSA identification. The capture and elution efficiencies for MRSA were optimized by examining factors such as incubation time, temperature, and elution solvents. The aptamer-modified magnetic nanoparticles showed a capture rate of more than 90% under the optimized condition, whereas the capture rates were less than 11% for non-target bacteria. The as-prepared nanoparticles exhibited only a 5% decrease in the capture rate and a 9% decrease in the elution rate after 10 successive cycles of utilization. Most importantly, the aptamer-modified nanoparticles revealed an excellent selectivity towards MRSA in bacterial mixtures. The capture of MRSA at a concentration of 102 CFU/mL remained at a good percentage of 82% even when the other two species were at 104 times higher concentration (106 CFU/mL). Further, the eluted MRSA bacteria were successfully identified using MALDI mass spectrometry.

Therapeutic Effect of a Newly Isolated Lytic Bacteriophage against Multi-Drug-Resistant Cutibacterium acnes Infection in Mice.

Acne vulgaris, which is mostly associated with the colonization of Cutibacterium acnes (C. acnes), is a common skin inflammatory disease in teenagers. However, over the past few years, the disease has extended beyond childhood to chronically infect approximately 40% of adults. While antibiotics have been used for several decades to treat acne lesions, antibiotic resistance is a growing crisis; thus, finding a new therapeutic target is urgently needed. Studies have shown that phage therapy may be one alternative for treating multi-drug-resistant bacterial infections. In the present study, we successfully isolated a C. acnes phage named TCUCAP1 from the skin of healthy volunteers. Morphological analysis revealed that TCUCAP1 belongs to the family Siphoviridae with an icosahedral head and a non-contractile tail. Genome analysis found that TCUCAP1 is composed of 29,547 bp with a G+C content of 53.83% and 56 predicted open reading frames (ORFs). The ORFs were associated with phage structure, packing, host lysis, DNA metabolism, and additional functions. Phage treatments applied to mice with multi-drug-resistant (MDR) C.-acnes-induced skin inflammation resulted in a significant decrease in inflammatory lesions. In addition, our attempt to formulate the phage into hydroxyethyl cellulose (HEC) cream may provide new antibacterial preparations for human infections. Our results demonstrate that TCUCAP1 displays several features that make it an ideal candidate for the control of C. acnes infections.