Synergistic antimicrobial system based on nisin and α-hydroxy organic acids.

Synergistic antimicrobial is a promising way to overcome microbial contamination in food and drugs. In the study, the synergistic effect between nisin and α-hydroxy organic acids on E. coli and S. aureus was investigated. The experimental results showed that the combined antibacterial ability of nisin-citric acid system was the most prominent. The FCI index also indicated that the combination of nisin and citric acid had synergistic effects on E. coli. When nisin was combined with citric acid, the inhibition rates of E. coli and S. aureus were increased to 4.43 and 1.49 times, respectively. Nisin-citric acid complex system could effectively slow down the proliferation of S. aureus and E. coli at lower concentrations, and can quickly destroy the cell membrane after 4 h of action. Therefore, the combination of nisin and citric acid is expected to be a potential solution for food and drug preservation.

Lowering glycemic levels via gastrointestinal tract factors: the roles of dietary fiber, polyphenols, and their combination.

Dietary fiber (DF) and polyphenols (DP) are typical blood sugar-lowering components, and both play distinct yet interconnected roles in exerting their blood sugar-lowering effects. We comprehensively summarized the single and combined effects of DF and DP on blood glucose homeostasis through regulating the relevant factors in the upper gastrointestinal tract (UGT) and lower gastrointestinal tract (LGT). In the UGT, DF slowed down glucose metabolism by enhancing digesta viscosity and hindering enzyme-substrate interaction. DP primarily targeted enzymes and substrates. When combined, DP enhanced the adsorption capacity of DF for glucose. DF weakened DP's inhibitory effect on enzymes. Both DF and DP disrupted glucose intestinal uptake via physical or genomic modulation, but the co-consumption of DF and DP demonstrated a lower inhibitory effect on glucose uptake than DP alone. In the LGT, DF and DP showed synergistic or antagonistic effects on gut microbiota. Remarkably, whole foods exhibited potent prebiotic effects due to their compound-rich matrix, potentially enhancing glucose homeostasis and expanding dietary options for glucose regulation research.

Investigation of the combined cytotoxicity induced by sodium butyrate and a flavonoid quercetin treatment on MCF-7 breast cancer cells.

Quercetin (QUE) belonging to the flavonoid class is a common phytochemical present in the daily diet of some individuals. Quercetin is an important source of free radical scavengers. This property makes this flavonoid a reliable antioxidant with the following properties: anti-inflammatory, anti-diabetic, antimicrobial and anti-carcinogenic. Sodium butyrate (NaBu) acts as a histone deacetylase inhibitor (HDACi) and is known to regulate apoptosis in cancer cells. Combining natural flavonoids such as QUE with different substances may synergistically enhance their anti-carcinogenic capacity. Thus, the aim of this study was to examine the combined treatment effects of QUE and NaBu in hormone-sensitive breast cancer cells in vitro. MCF-7 breast cancer cells were treated with QUE alone, NaBu alone, as well as QUE and NaBu combined to determine the following: cell proliferation, levels of protein annexin A5 (ANXA5) and reactive oxygen species (ROS), mRNA protein expression, as well as cell and nuclear morphology. Data demonstrated that either QUE or NaBu alone inhibited cell proliferation, and reduced levels protein ANXA5, ROS and mRNA protein expression, The combination of QUE and NaBu produced a significant synergistic inhibitory effect compared to treatment groups of QUE or NaBu alone. In conclusion, our findings showed that the combination treatment of QUE and NaBu may constitute a promising therapeutic approach to breast cancer treatment but this needs further molecular and in vivo investigations.

Improvement of the In Vitro Cytotoxic Effect on HT-29 Colon Cancer Cells by Combining 5-Fluorouacil and Fluphenazine with Green, Red or Brown Propolis.

Cancer is regard as one of the key factors of mortality and morbidity in the world. Treatment is mainly based on chemotherapeutic drugs that, when used in targeted therapies, have serious side effects. 5-fluorouracil (5-FU) is a drug commonly used against colorectal cancer (CRC), despite its side effects. Combination of this compound with natural products is a promising source in cancer treatment research. In recent years, propolis has become the subject of intense pharmacological and chemical studies linked to its diverse biological properties. With a complex composition rich in phenolic compounds, propolis is described as showing positive or synergistic interactions with several chemotherapeutic drugs. The present work evaluated the in vitro cytotoxic activity of the most representative propolis types, such as green, red and brown propolis, in combination with chemotherapeutic or CNS drugs on HT-29 colon cancer cell lines. The phenolic composition of the propolis samples was evaluated by LC-DAD-ESI/MSn analysis. According to the type of propolis, the composition varied; green propolis was rich in terpenic phenolic acids and red propolis in polyprenylated benzophenones and isoflavonoids, while brown propolis was composed mainly of flavonoids and phenylpropanoids. Generally, for all propolis types, the results demonstrated that combing propolis with 5-FU and fluphenazine successfully enhances the in vitro cytotoxic activity. For green propolis, the combination demonstrated an enhancement of the in vitro cytotoxic effect compared to green propolis alone, at all concentrations, while for brown propolis, the combination in the concentration of 100 µg/mL gave a lower number of viable cells, even when compared with 5-FU or fluphenazine alone. The same was observed for the red propolis combination, but with a higher reduction in cell viability. The combination index, calculated based on the Chou-Talalay method, suggested that the combination of 5-FU and propolis extracts had a synergic growth inhibitory effect in HT-29 cells, while with fluphenazine, only green and red propolis, at a concentration of 100 µg/mL, presented synergism.

An efficient CRISPR interference-based prediction method for synergistic/additive effects of novel combinations of anti-tuberculosis drugs.

Tuberculosis (TB) is treated by chemotherapy with multiple anti-TB drugs for a long period, spanning 6 months even in a standard course. In perspective, to prevent the emergence of antimicrobial resistance, novel drugs that act synergistically or additively in combination with major anti-TB drugs and, if possible, shorten the duration of TB therapy are needed. However, their combinatorial effect cannot be predicted until the lead identification phase of the drug development. Clustered regularly interspaced short palindromic repeats interference (CRISPRi) is a powerful genetic tool that enables high-throughput screening of novel drug targets. The development of anti-TB drugs promises to be accelerated by CRISPRi. This study determined whether CRISPRi could be applicable for predictive screening of the combinatorial effect between major anti-TB drugs and an inhibitor of a novel target. In the checkerboard assay, isoniazid killed Mycobacterium smegmatis synergistically or additively in combinations with rifampicin or ethambutol, respectively. The susceptibility to rifampicin and ethambutol was increased by knockdown of inhA, which encodes a target molecule of isoniazid. Additionally, knockdown of rpoB, which encodes a target molecule of rifampicin, increased the susceptibility to isoniazid and ethambutol, which act synergistically with rifampicin in the checkerboard assay. Moreover, CRISPRi could successfully predict the synergistic action of cyclomarin A, a novel TB drug candidate, with isoniazid or rifampicin. These results demonstrate that CRISPRi is a useful tool not only for drug target exploration but also for screening the combinatorial effects of novel combinations of anti-TB drugs. This study provides a rationale for anti-TB drug development using CRISPRi.

Combined effects of Scutellaria baicalensis with metformin on glucose tolerance of patients with type 2 diabetes via gut microbiota modulation.

Metformin is a widely prescribed antidiabetic agent, whereas Scutellaria baicalensis (SB) is a commonly used medicinal herb for treatment of type 2 diabetes (T2D). Gut microbiota is involved in pathophysiology of metabolic diseases including T2D, and intestinal microbiota may be one of the important therapeutic targets for the ailment. This study was conducted to investigate the effects of SB combined with metformin on treatment of T2D while evaluating changes in the gut microbiota composition. Patients with T2D were randomized into control and treatment groups. Subjects who had already been prescribed metformin were allotted to additional SB (3.52 g/day) group or placebo group. The initial treatment session was 8 wk, and after washout period for 4 wk they were crossed over to the opposite treatment for another 8 wk. The influence of SB and placebo on the intestinal microbiota was analyzed by MiSeq system based on 16S rRNA gene. Glucose tolerance was lower in the SB group than the placebo group. Similarly, the relative RNA expression of TNF-α was significantly reduced after SB treatment. SB treatment influenced the gut microbiota, especially Lactobacillus and Akkermansia, which showed remarkable increases after SB treatment. Some subjects showed high liver enzyme levels after SB treatment, and their microbiota composition at baseline differed with subjects whose liver enzymes were not affected. We also predicted that selenocompound metabolism was increased and naphthalene degradation was decreased after SB treatment. These results suggest that SB with metformin treatment may improve the glucose tolerance and inflammation and influence the gut microbiota community in T2D.

The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males.

We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.

Effects of combined oleic acid and fluoride at sub-MIC levels on EPS formation and viability of Streptococcus mutans UA159 biofilms.

Despite the widespread use of fluoride, dental caries, a biofilm-related disease, remains an important health problem. This study investigated whether oleic acid, a monounsaturated fatty acid, can enhance the effect of fluoride on extracellular polysaccharide (EPS) formation by Streptococcus mutans UA159 biofilms at sub-minimum inhibitory concentration levels, via microbiological and biochemical methods, confocal fluorescence microscopy, and real-time PCR. The combination of oleic acid with fluoride inhibited EPS formation more strongly than did fluoride or oleic acid alone. The superior inhibition of EPS formation was due to the combination of the inhibitory effects of oleic acid and fluoride against glucosyltransferases (GTFs) and GTF-related gene (gtfB, gtfC, and gtfD) expression, respectively. In addition, the combination of oleic acid with fluoride altered the bacterial biovolume of the biofilms without bactericidal activity. These results suggest that oleic acid may be useful for enhancing fluoride inhibition of EPS formation by S. mutans biofilms, without killing the bacterium.

Inhibition of C-terminal truncated PPM1D enhances the effect of doxorubicin on cell viability in human colorectal carcinoma cell line.

PPM1D is a p53-inducible Ser/Thr phosphatase. One of the main functions of PPM1D in normal cells is to act as a negative regulator of the p53 tumor suppressor by dephosphorylating p53 and several kinases. PPM1D is considered an oncoprotein owing to both its functions and the fact that gene amplification and overexpression of PPM1D are reported in several tumors. Recently, PPM1D mutations resulting in C-terminal truncated alterations were found in brainstem gliomas and colorectal cancers, and these mutations enhanced the activity of PPM1D. Therefore, C-terminal truncated PPM1D should be also considered as a potential candidate target of anticancer drugs. Here we showed that combination treatment with PPM1D-specific inhibitor SPI-001 and doxorubicin suppressed cell viability of HCT-116 cells overexpressing C-terminal truncated PPM1D through p53 activation compared with doxorubicin alone. Our results suggest that combination treatment with PPM1D inhibitor and doxorubicin may be a potential anti-cancer treatment in PPM1D-mutated cancer cells.

An evaluation of the combination effect of zoledronate and chemotherapeutic agents in canine osteosarcoma cells.

Introduction: Osteosarcoma (OSA) is an aggressive form of bone cancer in both dogs and humans. The treatment options for metastatic (stage III) OSA are currently limited and the prognosis is poor. Zoledronate, a second generation amino-bisphosphonate, is commonly used for palliation of cancer induced bone pain. Zoledronate has also demonstrated anti-cancer properties and possibly enhances the cytotoxicity of doxorubicin in a canine histiocytosis cell line and human prostatic cancer cell line. The goal of this study was to evaluate the combination effect of zoledronate and various chemotherapeutic drugs in canine OSA cells. Methods: Canine OSA cell line (D17), cells from two canine primary OSAs, and MDCK, a canine kidney cell line, were used to evaluate the therapeutic potential of these drugs. Carboplatin, doxorubicin, vinorelbine, toceranib, and isophosphoramide mustard (active metabolite of ifosfamide) were used as chemotherapeutic agents. First, cells were treated with either zoledronate or chemotherapy drug alone for 72 hours. Cell viability was assessed using CellTiter Glo and IC5, IC10, IC20, and IC50 were calculated. Second, cells were treated with a combination of zoledronate and each chemotherapeutic agent at their IC5, IC10, IC20, and IC50 concentrations. After 72 hours, cell viability was assessed by CellTiter Glo. Results and discussion: Zoledronate, carboplatin, doxorubicin, vinorelbine, and isophosphoramide mustard showed concentration dependent decrease in cell viability. Toceranib showed decreased cell viability only at higher concentrations. When zoledronate was used in combination with chemotherapy drugs, while it showed potential synergistic effects with toceranib, potential antagonistic effects with vinorelbine and isophosphoramide mustard were observed. However, the results differed by cell line and thus, further evaluation is warranted to understand the exact mechanism of action.

In vitro effects of N-acetylcysteine in combination with antifungal agents against Malassezia pachydermatis isolated from canine otitis externa.

BACKGROUND: Many clinicians prescribe antifungal agents to treat canine otitis externa (OE). However, studies evaluating the antifungal effects of N-acetylcysteine (NAC) and its combinations are limited. HYPOTHESIS/OBJECTIVES: The aim of this study was to evaluate the antifungal effects of NAC alone and in combination with other antifungal agents against Malassezia pachydermatis isolated from canine OE. MATERIALS AND METHODS: M. pachydermatis samples were collected from 13 dogs with OE. The final concentration of the inoculum suspensions of M. pachydermatis was 1-5 × 106 colony forming units/mL. The concentrations of the test compounds ketoconazole (KTZ), terbinafine (TER), nystatin (NYS) and NAC were 0.02-300 µg/mL, 0.04-80 µg/mL, 0.16-40 µg/mL and 1.25-20 mg/mL, respectively. The minimum inhibitory concentration (MIC) was measured to evaluate the susceptibility of the M. pachydermatis to KTZ, TER, NYS and NAC. The checkerboard testing method and fractional inhibitory concentration index were used to evaluate the effect of NAC in combination with KTZ, TER and NYS against M. pachydermatis. RESULTS: The MIC90 values of M. pachydermatis were 4.6875-9.375 µg/mL, 1.25 µg/mL, 5-10 µg/mL and 10 mg/mL for KTZ, TER, NYS and NAC, respectively. The synergistic effects of KTZ, TER and NYS with NAC were identified in 0/13, 2/13 and 0/13 isolates, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: NAC had an antifungal effect against M. pachydermatis but did not exert synergistic effects when used with KTZ, TER and NYS. Thus, the use of NAC alone as a topical solution could be considered an effective treatment option for canine OE involving M. pachydermatis.

Apoptosis-driven synergistic anti-cancer efficacy of ethyl acetate extract of Memecylon sisparense Gamble leaves and doxorubicin in in-vitro and in-vivo models of triple-negative breast cancer.

In the spectrum of breast neoplasms, approximately 15 to 20% of all diagnosed cases are triple-negative breast carcinoma. TNBC grows and spreads faster than other invasive breast cancers and has a worse prognosis. The existing therapies and chemotherapeutic drugs have several limitations, so the development of safe and affordable treatment options is currently in demand. Hence, this research focuses on scientifically evaluating the therapeutic anticancer effect of ethyl acetate extract of MSG and its combined efficacy with doxorubicin against TNBC. MSG has shown an IC50 value of 48.40 ± 1.68 µg/ml on the MDA-MB-231 cell line, and the combination of MSG with Dox demonstrated the synergistic effect. Apoptotic changes such as membrane blebbing chromatin condensation were observed in MSG alone and in combination with doxorubicin treatments. Apoptosis was confirmed with Annexin V-FITC/PI staining and increased apoptotic markers such as Cleaved caspase-3 Bax and decreased anti-apoptotic markers Bcl-2 by western blotting. The tumor burden significantly decreased in MSG and combination treatment groups while restoring their body weights. Meanwhile, the Dox-treated group indicated a decreased tumor burden combined with weight loss. The present investigation revealed that MSG and doxorubicin have a synergistic anticancer effect in TNBC.

Study of Antidiabetic Properties of Berberis asiatica and Withania somnifera in Streptozotocin-Nicotinamide-Induced Type II Diabetes Mellitus in Wistar Rats.

Background and aim Diabetes is a chronic metabolic disorder characterized by elevated blood glucose levels. Although current antidiabetic drugs are highly effective, they are associated with various adverse drug reactions, including life-threatening hypoglycemia, skin rashes, and gastrointestinal intolerance, in addition to being costly. This animal-based experimental study aims to develop a herbal alternative or adjuvant to current antidiabetic drugs using Berberis asiatica (BA) and Withania somnifera (WS), which could potentially have fewer adverse drug reactions and reduce the required dose of existing antidiabetic medications. Material and methods Seventy-eight adult albino Wistar rats weighing between 150 and 250 g were used for the study. Diabetes mellitus (DM) was induced by intraperitoneal (i.p) injections of streptozotocin (STZ) (65 mg/kg) 15 minutes after nicotinamide (NIC) (110 mg/kg) administration. As the diabetes was confirmed (blood glucose level > 250 mg/dL), rats were divided into 13 different groups mentioned. The standard antidiabetic drugs (metformin [MET] and glimepiride [GLI]) and polyherbal combinations (PHC) (BA + WS) were administered orally, individually (WS and BA), and in combination (BA + WS). Blood samples were collected for biochemical analysis using the tail vein prick method.  The study is based on a total of 13 groups, six rats in each group. Groups 1 and 2 (normal control [NC] and diabetic control [DC]) received distilled water at a dose of 10 mL/kg orally for 28 days. Groups 3-5 (BA 250, 500, and 1000) received dried ethanolic root extract of BA at a dose of 250, 500, and 1000 mg/kg orally, respectively, for 28 days. Groups 6-8 (WS 250, 500, and 1000) received dried ethanolic root extract of WS at a dose of 250, 500, and 1000 mg/kg orally, respectively, for 28 days. Groups 9-11 (PHC 250, 500, and 1000) received dried ethanolic root extract of BA + WS at a dose of 250, 500, and 1000 mg/kg orally, respectively, for 28 days. Groups 12 and 13 (MET and GLI) received standard drugs MET and GLI at a dose of 250 and 10 mg/kg orally, respectively, for 28 days. Results The dried ethanolic root extract of medicinal herbal plants BA and WS and their combination exhibited significant antidiabetic efficacy. PHC has been shown to have a superior antidiabetic effect than individuals. PHC 500 and 1000 showed blood glucose levels similar to those of the GLI group (P < 0.05). Additionally, PHC 1000 showed blood glucose levels similar to those of the MET group (P < 0.05). Conclusion Our results indicate that both BA and WS possess hypoglycemic activity, and their combination also has a synergistic antidiabetic effect compared to the individual extract. These findings are promising in developing new safe and cost-effective herbal combinations as alternatives or additives to currently used synthetic antidiabetic drugs.

Helicobacter pylori plus N-Methyl-N'-nitro-N-nitrosoguanidine: DNA damage and repair: Malignant transformation of human esophageal epithelial cells.

N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG), found in pickled foods and in chlorinated water, has been used to induce malignant transformation and gastrointestinal cancer in rats. Helicobacter pylori (HP) is implicated in human gastric cancer and possibly also in esophageal cancer. These two agents - one chemical and the other biological - might act together to induce esophageal cancer. In this study, human esophageal epithelial cells (HEECs) were divided into four groups: HP, MNNG, HP + MNNG, and control. The HP-to-HEEC ratio was 100:1. Cells were exposed for 6 h and then passaged until malignant transformation. HEEC at early, intermediate, and late stages of malignant transformation were used for proliferation, cell-cycle, and invasion assays. The alkaline comet assay was performed and expression of proteins, including γ-H2AX and PAXX, was studied by western blotting, to explore DNA damage and repair processes. Measurements of cell morphology, soft-agar clone formation, and invasiveness, and a nude mouse xenograft model, were used to examine malignancy. The effect of HP was stronger than that of MNNG. The combination HP + MNNG exerted a stronger malignant transformation effect than either HP or MNNG alone. Mechanisms of this combined carcinogenesis may include promotion of cell proliferation, perturbation of the cell cycle, promotion of invasiveness, DNA double-strand break induction, or PAXX inhibition.

Effect of a combined program of running exercise and environmental enrichment on memory function and neurogenesis markers in amyloid-beta-induced Alzheimer-like model.

Objectives: It is urgent to develop non-pharmacological interventions or multifactor combination approaches to combat Alzheimer's disease (AD). The effect of exercise (EX) combined with environmental enrichment (EE) on behavioral phenotypes and neurogenesis markers in an Alzheimer-like rat model was investigated. Materials and Methods: The groups consisted of AD, sham-operated, AD+EX, AD+EE, and AD+EX+EE. AD was produced by injection of amyloid-beta (1-42, 6 µg) intrahippocampally, and a daily treadmill for 3 consecutive weeks was used for EX animals. EE was a large cage (50× 50× 50 cm) containing differently shaped objects. Spatial learning and memory were evaluated in the Morris water maze (MWM), and a shuttle box was used to evaluate inhibitory avoidance memory. RT-PCR was performed to assess the expression of early neurogenesis markers, DCX, and Sox2 within the hippocampus. Results: Pretreatment with exercise and EE, both individually and in combination, could provide protection from memory impairments in AD rats. Combined treatment led to a significantly more pronounced improvement in memory deficits of AD rats than either paradigm alone. Combination therapy with exercise and EE could also reverse the passive avoidance memory impairment and hippocampal DCX expression of AD rats to the control levels. Conclusion: These data suggest that exercise in combination with cognitive engagement can provide a non-pharmacological and multidomain policy that may prevent or delay AD symptoms.

Metabolic risk factors link unhealthy lifestyles to the risk of colorectal polyps in China.

Colorectal cancer is the second leading cause of global cancer-related deaths, and its precursor lesions are colorectal polyps (CAP). The study aimed to explore the effect of combinations of unhealthy lifestyles on CAP and investigate the mediation role of metabolic disorder in this process. A total of 1299 adults were recruited from a hospital in Jiangsu, China, including 811 cases and 488 adults without diseases. The information on demographic characteristics and lifestyles was collected through questionnaires and the medical record system. Serum biochemical parameters were determined using the automatic biochemical analyzer. Adjusted regression analysis showed that unhealthy lifestyles, including smoking, overnight meals, daily water intake, staying up late, and exercise associated with the risk of CAP. Furthermore, metabolic biomarkers, including BMI, triglycerides, and uric acid, were associated with the risk of CAP. Also, unhealthy lifestyle scores were positively associated with BMI, triglycerides, and CAP. The mediation effect of metabolic biomarkers, such as BMI and triglycerides on the association of unhealthy lifestyle scores with CAP was significant. Available data demonstrate the adverse effect of combinations of unhealthy lifestyle factors on CAP, and metabolic disorders to potentially mediate the association of unhealthy lifestyles with the risk of CAP.

Functional metabolism pathways of significantly regulated genes in Nannochloropsis oceanica with various nitrogen/phosphorus nutrients for CO2 fixation.

To determine the optimal CO2 concentration for microalgal biomass cultivated with industrial flue gas and improve carbon fixation capacity and biomass production. Functional metabolism pathways of significantly regulated genes in Nannochloropsis oceanica (N. oceanica) with various nitrogen/phosphorus (N/P) nutrients for CO2 fixation were comprehensively clarified. At 100 % N/P nutrients, the optimum CO2 concentration was 70 % and the maximum biomass production of microalgae was 1.57 g/L. The optimum CO2 concentration was 50 % for N or P deficiency and 30 % for both N and P deficiency. The optimal combination of CO2 concentration and N/P nutrients caused significant up regulation of proteins related to photosynthesis and cellular respiration in the microalgae, enhancing photosynthetic electron transfer efficiency and carbon metabolism. Microalgal cells with P deficiency and optimal CO2 concentration expressed many phosphate transporter proteins to enhance P metabolism and N metabolism to maintain a high carbon fixation capacity. However, inappropriate combination of N/P nutrients and CO2 concentrations caused more errors in DNA replication and protein synthesis, generating more lysosomes and phagosomes. This inhibited carbon fixation and biomass production in the microalgae with increased cell apoptosis.

The Combined Effects of Sublingual Immunotherapy and Lactobacillus acidophilus-Producing Extract on Cedar Pollinosis Symptoms.

INTRODUCTION: Sublingual immunotherapy (SLIT), in which standardized cedar pollen extract solution is administered, has been used to treat cedar pollinosis, but SLIT is problematic because it takes a long time to become effective, and some cases are ineffective even after long-term treatment. It has also been reported that lactobacillus acidophilus extract (LEX), a food-derived ingredient, alleviates various allergic symptoms. This study examined the usefulness of LEX as a treatment for cedar pollinosis in comparison with SLIT. We also examined whether the combined use of SLIT and LEX could have an early-onset of therapeutic effect on cedar pollinosis. We also examined the usefulness of LEX as a salvage therapy for patients who failed to respond to SLIT. SUBJECTS AND METHODS: Fifteen patients with cedar pollinosis were divided into three groups. The three groups were: three patients in the standardized cedar pollen extract group (S group), seven patients in the lactobacillus-producing extract group (L group), and five patients in the combination group of standardized cedar pollen extract and lactobacillus-producing extract (SL group). The subjects were treated for three years, corresponding to the three scattering seasons of cedar pollen, and observed according to the evaluation items. The evaluation items were severity score based on examination findings, subjective symptom score (QOL score) based on the Japanese Standard QOL Questionnaire for Allergic Rhinitis (JRQLQ No. 1) questionnaire, nonspecific IgE level measurement by blood test, and cedar pollen-specific IgE level measurement. RESULTS: After three years of observation, there were no significant differences in severity score and nonspecific IgE levels among the three groups, while QOL score decreased significantly between the first and third years of treatment in the L group. Cedar pollen-specific IgE levels in the S and SL groups showed an increase in the first year and a gradual decrease in the second and third years of treatment compared to the pre-treatment period. In group L, no increase was observed in the first year, and a significant decrease was observed in the second and third years during the cedar pollen dispersal period. CONCLUSIONS: The results of severity and quality of life scores indicated that it took three years of treatment for the S and SL groups to show efficacy, while the L group showed improvement in quality of life scores and cedar pollen-specific IgE levels from the first year, suggesting that LEX is useful as a treatment for cedar pollinosis. The efficacy of combination therapy with SLIT and LEX was not clear, but since the effect of LEX was observed from the early stage of treatment, it was thought that the combination therapy with LEX intake from the early stage of treatment may be effective in reducing the incidence of ineffective cases. The combination therapy of SLIT and LEX may also be useful as a salvage therapy.

Combination Treatment for Inhibition of the Growth of Staphylococcus aureus with Recombinant SAP8 Endolysin and Nisin.

Staphylococcus aureus, a pathogenic species of genus Staphylococcus involved in foodborne illness always remain among the top priorities of the world major concerns. In the present study, we have used recombinant SAP8 endolysin from the bacteriophage SAP8 and commercial nisin to inhibit the viability of pathogenic S. aureus KCTC 3881 cells; however, the approach was not identified as cost-effective. A gradual decrease in the viable S. aureus KCTC 3881 cell counts was observed with an increase in the concentrations of recombinant SAP8 endolysin and nisin. However, combined treatment with recombinant SAP8 endolysin and nisin decreased the viable S. aureus KCTC 3881 cell counts in a significant manner. The combination of 0.01 µM of recombinant SAP8 endolysin with 9 IU/mL and 18 IU/mL of nisin demonstrated a promising decrease in the viable cell counts of the strain. Under the scanning electron microscope, the combination treatment with 0.01 µM of recombinant SAP8 endolysin and 18 IU/mL of nisin showed complete cellular destruction of S. aureus KCTC 3881. We propose that a combination of recombinant SAP8 endolysin and nisin could be a strong alternative to antibiotics to control the growth of S. aureus including MRSA.

Associations of multi-faceted factors and their combinations with frailty in Japanese community-dwelling older adults: Kashiwa cohort study.

PURPOSE: To investigate the cross-sectional associations of nutrition-related, physical, and social factors and their combinations with frailty in community-dwelling older adults. METHODS: The participants in this study were 1,161 adults (≥ 65 years). The outcome was frailty severity as assessed by the Cardiovascular Health Study index (score 0: no-frailty, score 1-2: pre-frailty, score ≥ 3: frailty). The independent variables included nutrition-related factors comprising a balanced diet and oral functions, physical factors including exercise habits and awareness of physical function, and social factors including social organizational participation, social support, and social networks. According to the quantity of factors the participants met, four groups were divided. An ordinal logistic regression analysis was conducted to evaluate the associations between frailty severity and the three factors individually and comprehensively. RESULTS: The mean age was 74.6 (±5.4) and the women is 47.8%. 47.7% and 8.7% of participants had pre-frailty or frailty respectively. Meeting no nutrition-related, physical, or social factors individually showed significantly associated with greater adjusted odds ratio (aORs) of frailty severity [aORs (95% confidence interval)]: nutrition-related factors: 1.58 [1.25-2.01]; physical factors: 2.53 [1.98-3.22]; social factors: 1.52 [1.19-1.93]. Referred to participants who met three factors, participants who met two, one, or none showed significantly associated with increased aORs of frailty severity: two: 1.88 [1.34-2.65]; one: 2.97 [2.09-4.23]; none: 7.52 [4.87-11.62]. CONCLUSION: Meeting no nutrition-related, physical, or social factors individually showed higher risk of being (pre-)frailty. Meeting three factors showed lowest risk of being (pre-)frailty and this risk increased with the quantity decreasing of met factors.