Cysteine-binding adjuvant enhances survival and promotes immune function in a murine model of acute myeloid leukemia.

ABSTRACT: Therapeutic vaccination has long been a promising avenue for cancer immunotherapy but is often limited by tumor heterogeneity. The genetic and molecular diversity between patients often results in variation in the antigens present on cancer cell surfaces. As a result, recent research has focused on personalized cancer vaccines. Although promising, this strategy suffers from time-consuming production, high cost, inaccessibility, and targeting of a limited number of tumor antigens. Instead, we explore an antigen-agnostic polymeric in situ cancer vaccination platform for treating blood malignancies, in our model here with acute myeloid leukemia (AML). Rather than immunizing against specific antigens or targeting adjuvant to specific cell-surface markers, this platform leverages a characteristic metabolic and enzymatic dysregulation in cancer cells that produces an excess of free cysteine thiols on their surfaces. These thiols increase in abundance after treatment with cytotoxic agents such as cytarabine, the current standard of care in AML. The resulting free thiols can undergo efficient disulfide exchange with pyridyl disulfide (PDS) moieties on our construct and allow for in situ covalent attachment to cancer cell surfaces and debris. PDS-functionalized monomers are incorporated into a statistical copolymer with pendant mannose groups and TLR7 agonists to target covalently linked antigen and adjuvant to antigen-presenting cells in the liver and spleen after IV administration. There, the compound initiates an anticancer immune response, including T-cell activation and antibody generation, ultimately prolonging survival in cancer-bearing mice.

Cellular Mechanisms Underlying the Cardioprotective Role of Allicin on Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are a group of diseases in which the common denominator is the affection of blood vessels, heart tissue, and heart rhythm. The genesis of CVD is complex and multifactorial; therefore, approaches are often based on multidisciplinary management and more than one drug is used to achieve the optimal control of risk factors (dyslipidemia, hypertension, hypertrophy, oxidative stress, endothelial dysfunction, inflammation). In this context, allicin, a sulfur compound naturally derived from garlic, has shown beneficial effects on several cardiovascular risk factors through the modulation of cellular mechanisms and signaling pathways. Effective pharmacological treatments for CVD or its risk factors have not been developed or are unknown in clinical practice. Thus, this work aimed to review the cellular mechanisms through which allicin exerts its therapeutic effects and to show why it could be a therapeutic option for the prevention or treatment of CVD and its risk factors.

Anticancer potential of allicin: A review.

Phytochemicals have attracted attention in the oncological field because they are biologically friendly and have relevant pharmacological activities. Thanks to the intense and unique spicy aroma, garlic is one of the most used plants for cooking. Its consumption is correlated to health beneficial effects towards several chronic diseases, such as cancer, mainly attributable to allicin, a bioactive sulfur compound stored in different plant parts in a precursor form. The objective of this review is to present and critically discuss the chemistry and biosynthesis of allicin, its pharmacokinetic profile, its anticancer mechanisms and molecular targets, and its selectivity towards tumor cells. The research carried out so far revealed that allicin suppresses the growth of different types of tumors. In particular, it targets many signaling pathways associated with cancer development. Future research directions are also outlined to further characterize this promising natural product.

Parasitological and Biochemical Efficacy of the Active Ingredients of Allium sativum and Curcuma longa in Schistosoma mansoni Infected Mice.

The active ingredients allicin and curcumin have a wide range of actions against fungi, bacteria, and helminths. Therefore, the study was aimed to evaluate the efficacy of allicin (AL) and curcumin (CU) as antischistosomal drugs and their biochemical effects in normal and Schistosoma mansoni-infected mice. Praziquantel (PZQ) was administrated for two successive days while AL or CU was given for two weeks from the week 7th postinfection (PI). The possible effect of different regimens on Schistosoma worms was evaluated by measuring the percentage of the recovered worms, tissue egg load, and oogram pattern. Serum alanine transaminase activity and levels of triglycerides, cholesterol, and uric acid were measured. Liver tissue malondialdehyde and reduced glutathione levels besides, the activities of glutathione-S-transferase, superoxide dismutase and catalase were assessed for the oxidative/antioxidant condition. DNA electrophoresis of liver tissue was used to indicate the degree of fragmentation. There was a significant reduction in the recovered worms and egg load, with a marked change of oogram pattern in all treated groups with PZQ, AL, and CU in comparison with infected-untreated mice. PZQ, AL, and CU prevented most of the hematological and biochemical disorders, as well as significantly improved the antioxidant capacity and enhanced DNA fragmentation in the liver tissue of schistosomiasis mice compared to the infected-untreated group. These promising results suggest that AL and CU are efficient as antischistosomal drugs, and it would be beneficial to test their combination to understand the mechanism of action and the proper period of treatment leading to the best result.

Anti-Inflammatory Effect of Allicin Associated with Fibrosis in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling. Recent evidence supports that inflammation plays a key role in triggering and maintaining pulmonary vascular remodeling. Recent studies have shown that garlic extract has protective effects in PAH, but the precise role of allicin, a compound derived from garlic, is unknown. Thus, we used allicin to evaluate its effects on inflammation and fibrosis in PAH. Male Wistar rats were divided into three groups: control (CON), monocrotaline (60 mg/kg) (MCT), and MCT plus allicin (16 mg/kg/oral gavage) (MCT + A). Right ventricle (RV) hypertrophy and pulmonary arterial medial wall thickness were determined. IL-1ß, IL-6, TNF-α, NFκB p65, Iκß, TGF-ß, and α-SMA were determined by Western blot analysis. In addition, TNF-α and TGF-ß were determined by immunohistochemistry, and miR-21-5p and mRNA expressions of Cd68, Bmpr2, and Smad5 were determined by RT-qPCR. Results: Allicin prevented increases in vessel wall thickness due to TNF-α, IL-6, IL-1ß, and Cd68 in the lung. In addition, TGF-ß, α-SMA, and fibrosis were lower in the MCT + A group compared with the MCT group. In the RV, allicin prevented increases in TNF-α, IL-6, and TGF-ß. These observations suggest that, through the modulation of proinflammatory and profibrotic markers in the lung and heart, allicin delays the progression of PAH.

Thioacetamide-induced acute hepatic encephalopathy: central vs peripheral effect of Allicin.

Hepatic encephalopathy (HE) is a debilitating and life-threatening disease. Results from acute or chronic liver failure and is characterized by abnormal cerebral and neurological alterations. This study aimed at investigating the effect of allicin, the major functional component in freshly crushed garlic extract, on thioacetamide (TAA)-induced HE in rats. Induction of HE by a single dose of TAA (300 mg/kg; I.P.) was associated with a marked elevation in the serum levels of alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, total protein, blood urea nitrogen and serum ammonia besides reduction in the serum level of albumin. Moreover, it was accompanied with an increase in the hepatic and brain levels of inflammatory mediators; TNF-α and IL-1ß as well as elevation of the hepatic and brain levels of oxidative stress biomarkers; reduced glutathione and lipid peroxidation evidenced by malondialdeyde. Oral administration of allicin (50, 100 and 200 mg/kg; P.O.) for 6 days prior to TAA injection restored the serum liver function, hepatic and brain levels of inflammatory mediators as well as oxidative stress biomarkers in a dose-dependent manner. From our results, it can be concluded that allicin has a protective effect on TAA-induced HE in rats in a dose-dependent manner due to its powerful antioxidant and anti-inflammatory properties.

2D LDH-MoS2 clay nanosheets: synthesis, catalase-mimic capacity, and imaging-guided tumor photo-therapy.

Owing to the hypoxia status of the tumor, the reactive oxygen species (ROS) production during photodynamic therapy (PDT) of the tumor is less efficient. Herein, a facile method which involves the synthesis of Mg-Mn-Al layered double hydroxides (LDH) clay with MoS2 doping in the surface and anionic layer space of LDH was presented, to integrate the photo-thermal effect of MoS2 and imaging and catalytic functions of Mg-Mn-Al LDH. The designed LDH-MoS2 (LMM) clay composite was further surface-coated with bovine serum albumin (BSA) to maintain the colloidal stability of LMM in physiological environment. A photosensitizer, chlorin e6 (Ce6), was absorbed at the surface and anionic layer space of LMM@BSA. In the LMM formulation, the magnetic resonance imaging of Mg-Mn-Al LDH was enhanced thanks to the reduced and acid microenvironment of the tumor. Notably, the ROS production and PDT efficiency of Ce6 were significantly improved, because LMM@BSA could catalyze the decomposing of the overexpressed H2O2 in tumors to produce oxygen. The biocompatible LMM@BSA that played the synergism with tumor microenvironment is a promising candidate for the effective treatment of cancer.

Diallyl Disulfide Suppresses Inflammatory and Oxidative Machineries following Carrageenan Injection-Induced Paw Edema in Mice.

Diallyl disulfide (DADS) is the major organosulfur constituent in garlic, with a variety of pharmacological activities including antioxidant and anti-inflammatory. Here, we examined the potential antiedematous impact of DADS- versus carrageenan-mediated paw edema in mice. Carrageenan injection potentiated an inflammatory reaction as presented by the elevated serological C-reactive protein (CRP) levels and transcription of tumor necrosis factor-alpha (TNF-α, Tnfα), interleukin-1 beta (IL-1ß, Il1b), interleukin-2 (IL-2, Il2), inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX-2, Ptgs2), prostaglandin E2 (PGE2), monocyte chemoattractant protein-1 (MCP-1, Ccl1), nuclear factor kappa B (NF-κB), and myeloperoxidase (MPO) activity, while interleukin-10 (IL-10) was declined in the injured paw tissue. Additionally, carrageenan elevated lipid peroxidation in terms of malondialdehyde (MDA) and decreased glutathione content (GSH). Remarkably, DADS was found to inhibit the inflammatory signaling, suppressed the developed oxidative damage, and protected the histopathological alterations in the inflamed paw tissue in response to carrageenan injection. Our findings suggest that DADS could be used as an alternative therapy used to alleviate the pathophysiological changes associated with the genesis of paw edema through its potent anti-inflammatory and antioxidant impacts.

Multifunctional molybdenum disulfide-copper nanocomposite that enhances the antibacterial activity, promotes rice growth and induces rice resistance.

Molybdenum disulfide sheets loaded with copper nanoparticles (MoS2-CuNPs) was prepared and its antibacterial activity against phytopathogen Xanthomonas oryzae pv. oryzae (Xoo) was investigated in vitro and in vivo for the first time. In a 2 h co-incubation, MoS2-CuNPs exhibited 19.2 times higher antibacterial activity against Xoo cells than a commercial copper bactericide (Kocide 3000). In the detached leaf experiment, the disease severity decreased from 86.25 % to 7.5 % in the MoS2-CuNPs treated rice leaves. The results further demonstrated that foliar application of MoS2-CuNPs could form a protective film and increase the density of trichome on the surface of rice leaves, finally prevent the infection of Xoo cells. This was probably due to the synergistic effect of MoS2-CuNPs. Additionally, foliar application of MoS2-CuNPs (4-32 µg/mL) increased obviously the content of Mo and chlorophyll (up 30.85 %), and then improved the growth of rice seedlings. Furthermore, the obtained MoS2-CuNPs could activate the activities of the antioxidant enzymes in rice, indicating higher resistance of rice under abiotic/biotic stresses. The multifunctional MoS2-CuNPs with superior antibacterial activity provided a promising alternative to the traditional antibacterial agents and had great potential in plant protection.

Z-ajoene from Crushed Garlic Alleviates Cancer-Induced Skeletal Muscle Atrophy.

Skeletal muscle atrophy is one of the major symptoms of cancer cachexia. Garlic (Allium sativum), one of the world's most commonly used and versatile herbs, has been employed for the prevention and treatment of diverse diseases for centuries. In the present study, we found that ajoene, a sulfur compound found in crushed garlic, exhibits protective effects against muscle atrophy. Using CT26 tumor-bearing BALB/c mice, we demonstrate in vivo that ajoene extract alleviated muscle degradation by decreasing not only myokines secretion but also janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) and SMADs/forkhead box (FoxO) signaling pathways, thereby suppressing muscle-specific E3 ligases. In mouse skeletal myoblasts, Z-ajoene enhanced myogenesis as evidenced by increased expression of myogenic markers via p38 mitogen-activated protein kinase (MAPK) activation. In mature myotubes, Z-ajoene protected against muscle protein degradation induced by conditioned media from CT26 colon carcinoma cells, by suppressing expression of muscle specific E3 ligases and nuclear transcription factor kappa B (NF-κB) phosphorylation which contribute to muscle atrophy. Moreover, Z-ajoene treatment improved myofiber formation via stimulation of muscle protein synthesis. These findings suggest that ajoene extract and Z-ajoene can attenuate skeletal muscle atrophy induced by cancer cachexia through suppressing inflammatory responses and the muscle wasting as well as by promoting muscle protein synthesis.

Diallyl disulfide attenuates non­alcoholic steatohepatitis by suppressing key regulators of lipid metabolism, lipid peroxidation and inflammation in mice.

Non­alcoholic steatohepatitis (NASH) is a common clinicopathological condition. Currently, the pathogenesis of NASH remains unknown, and no optimal therapy option currently exists. It has previously been demonstrated that diallyl disulfide (DADS) was capable of attenuating liver dysfunction, as DADS supplementation had a positive impact on liver regeneration, proliferation and oxidative damage. Thus, DADS could serve as a potential therapeutic agent that can protect against the effects of NASH. The present study aimed to evaluate the effect of DADS on NASH and to understand the associated underlying molecular mechanisms. A methionine­ and choline­deficient diet (MCD) and high­fat diet (HFD) are the two common animal models that induce NASH. C57BL/6J mice were fed an MCD for 4 weeks, or an HFD for 20 weeks, in the present study. The mice were treated with or without DADS (20, 50 and 100 mg/kg) for 4 or 20 weeks. For the histopathological examination, hematoxylin and eosin staining, oil red O staining and immunohistochemical analyses were performed using the liver sections. Biochemical assays and ELISA were performed to measure the serum biochemical indicators of hepatic function and inflammatory indicators, respectively. Reverse transcription­quantitative PCR, immunofluorescence and western blotting were used to detect expression levels of the genes involved in the molecular mechanisms underlying DADS protection. MCD or HFD induced the histological features of NASH in mice, including significant vacuolated hepatocytes, marked inflammatory cell infiltration and severe micro­ and macro­vesicular steatosis. Serum alanine transferase and aspartate aminotransferase levels, as well as the contents of liver triglyceride and total cholesterol, were significantly increased in these two models. DADS attenuated these histological and biochemical changes. DADS ameliorated hepatic steatosis by regulating sterol regulatory element­binding transcription factor 1, apolipoprotein A1, cyclic AMP­responsive element­binding protein H and fibroblast growth factor 21. Furthermore, DADS was revealed to prevent lipotoxicity via peroxisome proliferator­activated receptor α elevation and stearoyl­coenzyme A desaturase 1 inhibition in HFD­fed mice. In addition, DADS markedly inhibited lipid peroxidation by modulating malondialdehyde and superoxide dismutase, and it also decreased tumor necrosis factor­α production, interleukin­6 production and macrophage influx, as well as suppressing nuclear factor­κB activation, indicating suppression of MCD­induced hepatic inflammation. Taken together, the results have shown that DADS exerts beneficial effects on MCD­ or HFD­induced NASH by suppressing key regulators of lipid metabolism, lipid peroxidation and inflammation.

The garlic compound ajoene covalently binds vimentin, disrupts the vimentin network and exerts anti-metastatic activity in cancer cells.

BACKGROUND: Garlic has been used for centuries for its flavour and health promoting properties that include protection against cancer. The vinyl disulfide-sulfoxide ajoene is one of the phytochemicals found in crushed cloves, hypothesised to act by S-thiolating reactive cysteines in target proteins. METHODS: Using our fluorescently labelled ajoene analogue called dansyl-ajoene, ajoene's protein targets in MDA-MB-231 breast cancer cells were tagged and separated by 2D electrophoresis. A predominant band was identified by MALDI-TOF MS/MS to be vimentin. Target validation experiments were performed using pure recombinant vimentin protein. Computational modelling of vimentin bound to ajoene was performed using Schrödinger and pKa calculations by Epik software. Cytotoxicity of ajoene in MDA-MB-231 and HeLa cells was measured by the MTT assay. The vimentin filament network was visualised in ajoene-treated and non-treated cells by immunofluorescence and vimentin protein expression was determined by immunoblot. The invasion and migration activity was measured by wound healing and transwell assays using wildtype cells and cells in which the vimentin protein had been transiently knocked down by siRNA or overexpressed. RESULTS: The dominant protein tagged by dansyl-ajoene was identified to be the 57 kDa protein vimentin. The vimentin target was validated to reveal that ajoene and dansyl-ajoene covalently bind to recombinant vimentin via a disulfide linkage at Cys-328. Computational modelling showed Cys-328 to be exposed at the termini of the vimentin tetramer. Treatment of MDA-MB-231 or HeLa cells with a non-cytotoxic concentration of ajoene caused the vimentin filament network to condense; and to increase vimentin protein expression. Ajoene inhibited the invasion and migration of both cancer cell lines which was found to be dependent on the presence of vimentin. Vimentin overexpression caused cells to become more migratory, an effect that was completely rescued by ajoene. CONCLUSIONS: The garlic-derived phytochemical ajoene targets and covalently modifies vimentin in cancer cells by S-thiolating Cys-328. This interaction results in the disruption of the vimentin filament network and contributes to the anti-metastatic activity of ajoene in cancer cells.

Bottom-up synthesis of MoS2 nanospheres for photothermal treatment of tumors.

Photothermal therapy (PTT) is providing new opportunities for killing cancer cells. In this work, we introduce a new nanomedicine based on spherical MoS2 nanoparticles for PTT treatment of tumors, prepared using "green" bottom-up technology. To increase water solubility and avoid rapid clearance by the reticuloendothelial system, polyethylene glycol (PEG) was used to coat them. These MoS2-PEG nanospheres with an appropriate size (∼100 nm) exhibit high photothermal conversion efficiency (26.7%). In vitro cellular studies revealed that the MoS2-PEG nanospheres showed negligible cytotoxicity. Additionally, through combining the MoS2-PEG nanosphere samples with NIR irradiation at 808 nm, excellent in vitro tumor cell killing efficacy was achieved. In the 4T1 tumor model, the MoS2-PEG nanospheres exhibited good antitumor efficiency in vivo, displaying complete tumor inhibition over 16 days after treatment. Therefore, MoS2-PEG nanospheres played an important role in tumor destruction, and this concept for developing spherical MoS2-based nanomedicines can serve as a platform technology for the next generation of in vivo PTT agents.

Multifunctional Nanoflowers for Simultaneous Multimodal Imaging and High-Sensitivity Chemo-Photothermal Treatment.

Liver cancer is currently among the most challenging cancers to diagnose and treat. It is of prime importance to minimize the side effects on healthy tissues and reduce drug resistance for precise diagnoses and effective treatment of liver cancer. Herein, we report a facile but high-yield approach to fabricate a multifunctional nanomaterial through the loading of chitosan and metformin on Mn-doped Fe3O4@MoS2 nanoflowers. Mn-doped Fe3O4 cores are used as simultaneous T1/T2 magnetic resonance imaging (MRI) agents for sensitive and accurate cancer diagnosis, while MoS2 nanosheets are used as effective near-infrared photothermal conversion agents for potential photothermal therapy. The surface-functionalized chitosan was able not only to improve the dispersibility of Mn-doped Fe3O4@MoS2 nanoflowers in biofluids and increase their biocompatibility, but also to significantly enhance the photothermal effect. Furthermore, metformin loading led to high suppression and eradication of hepatoma cells when photothermally sensitized, but exhibited negligible effects on normal liver cells. Due to its excellent combination of T1/T2 MRI properties with sensitive chemotherapeutic and photothermal effects, our study highlights the promise of developing multifunctional nanomaterials for accurate multimodal imaging-guided, and highly sensitive therapy of liver cancer.

Antiarthritic Activity of Diallyl Disulfide against Freund's Adjuvant-Induced Arthritic Rat Model.

Diallyl disulfide (DADS) is an organosulfur compound derived mainly from garlic and genus Allium plants, which possess diverse biological properties. The aim of the present study was to evaluate the antiarthritic activity of DADS in rats with arthritis induced using complete Freund's adjuvant (CFA). DADS (20 mg/kg and 50 mg/kg) was administered and tested against CFA-induced arthritic rats by assessing various parameters: body weight, paw volume, arthritic score, organ indices (spleen and thymus), hematological and biochemical parameters, and proinflammatory cytokines. Histopathological analyses were also performed. The treatment of rats with DADS provoked significant reductions in paw volume, edema formation, arthritic score, and organ indices, together with significant improvement in body weight. DADS treatment also improved joint destruction and reduced inflammation, which was supported by histopathological studies. DADS significantly reduced the white blood cell count and improved red blood cell count in CFA-induced rats. The anti-arthritic activity in the CFA-induced rats was further confirmed by biochemical analysis. These findings suggest that DADS prevented cartilage destruction, improved health status, and reduced inflammation by decreasing the expression of proinflammatory cytokines in arthritis-induced rats. Hence, DADS may be a potential therapeutic candidate for the treatment of rheumatoid arthritis.

[Effect of Kangfuxin liquid combined with Garlicin Capsules in treatment of children with recurrent oral ulcer and on immune regulation].

PURPOSE: To study the effect of Kangfuxin liquid combined with Garlicin Capsules in treatment of children with recurrent oral ulcer (ROU) and on immunological regulation. METHODS: This randomized controlled clinical study prospectively enrolled 204 patients with ROU who were randomly divided into 2 groups. Patients in group A received Garlicin Capsules 1/time, 3 times/d, combined with Kangfuxin liquid 10 mL to gargle 3 times/d; patients in group B only received Kangfuxin liquid 10 mL gargle 5 min, 3/d. The treatment lasted for 2 weeks. The curative effect was compared before and after treatment, including ulcer surface pain (VAS score), time of ulcer healing, and the changes of T cell subsets (CD3+, CD4+, CD8+ and CD4+/CD8+) before and after treatment were compared by SPSS 22 software package. RESULTS: Ulcer healing time (3.5±0.6) d, duration of pain (3.1±0.3)d in group A were shorter than in group B (P<0.05); treatment efficiency was 96.08% in group A, 88.24% in group B( χ2=6.264, P<0.05). The pain scores of both groups were significantly reduced after treatment, and the difference was significant between group A and group B [(1.1±0.4) vs (3.2± 0.6)] (P<0.05). The levels of CD3+, CD4+, CD4+/CD8+ in group A were significantly higher than those in group A after treatment (P<0.05), the levels of CD8+ was significant lower than in group B (P<0.05). CONSLUSIONS: Kangfuxin liquid combined with Garlicin Capsules can improve the therapeutic effect of ROU and repair of local damaged mucosa in children, increasing the immune function of children.

Evaluation of Effect of Garlic Aged Extracts and Vitamin B12 on Noise-Induced Hearing Loss.

OBJECTIVE: This study investigated effects of S-allylmercaptocysteine (SAMC), diallyl disulfide (DADS), and vitamin B12 on inner ear functions and morphology after long-period high-level broadband noise exposure. MATERIALS AND METHODS: Twenty-four healthy rats were randomly divided into four groups. First group was chosen as the control group. Vitamin B12, SAMC, and DADS were applied to other groups for 4 weeks. On the 14th day, each group was exposed to broadband noise. Auditory brainstem response test was performed before and immediately after noise exposure and repeated on the 2nd and 14th day. RESULTS: Permanent threshold shifts were significantly lower in groups treated with vitamin B12, SAMC, and DADS. Histologically, cochleae of SAMC and DADS groups were found to be better preserved than the cochleae of vitamin B12 and control groups. CONCLUSION: Physiologically and histologically, SAMC and DADS reduced the long-term effects of noise. However, physiological recovery was not consistent with the morphological findings in vitamin B12 group.

Effect of diallyl disulfide on acute gastric mucosal damage induced by alcohol in rats.

This study investigated the gastroprotective effects of diallyl disulfide (DADS), a secondary organosulfur compound derived from garlic (Allium sativum L.) on experimental model of ethanol (EtOH)-induced gastric ulcer in rats. The antiulcerogenic activity of DADS was evaluated by gross/histopathological inspection, pro-inflammatory cytokines, and lipid peroxidation with antioxidant enzyme activities in the stomach. DADS (100 mg/kg) was administered by oral gavage 2 h prior to EtOH treatment (5 ml/kg). The animals were killed 1 h after receiving EtOH treatment. Pretreatment with DADS attenuated EtOH-induced gastric mucosal injury, as evidenced by decreased severity of hemorrhagic lesions and gastric ulcer index upon visual inspection. DADS also prevented histopathological alterations and gastric apoptotic changes caused by EtOH. An increase in tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase was observed in the gastric tissues of EtOH-treated rats that coincided with increased serum TNF-α and interleukin 6 levels. In contrast, DADS effectively suppressed production of pro-inflammatory mediators induced by EtOH. Furthermore, DADS prevented the formation of gastric malondialdehyde and the depletion of reduced glutathione content and restored antioxidant enzyme activities, such as catalase, glutathione peroxidase, and glutathione reductase in the gastric tissues of EtOH-treated rats. These results indicate that DADS prevents gastric mucosal damage induced by acute EtOH administration in rats and that the protective effects of DADS may be due to its potent antioxidant and anti-inflammatory activities.

Combined photothermal and photodynamic therapy delivered by PEGylated MoS2 nanosheets.

Single- or few-layered transitional metal dichalcogenides, as a new genus of two-dimensional nanomaterials, have attracted tremendous attention in recent years, owing to their various intriguing properties. In this study, chemically exfoliated MoS2 nanosheets are modified with lipoic acid-terminated polyethylene glycol (LA-PEG), obtaining PEGylated MoS2 (MoS2-PEG) with high stability in physiological solutions and no obvious toxicity. Taking advantage of its ultra-high surface area, the obtained MoS2-PEG is able to load a photodynamic agent, chlorin e6 (Ce6), by physical adsorption. In vitro experiments reveal that Ce6 after being loaded on MoS2-PEG shows remarkably increased cellular uptake and thus significantly enhanced photodynamic therapeutic efficiency. Utilizing the strong, near-infrared (NIR) absorbance of the MoS2 nanosheets, we further demonstrate photothermally enhanced photodynamic therapy using Ce6-loaded MoS2-PEG for synergistic cancer killing, in both in vitro cellular and in vivo animal experiments. Our study presents a new type of multifunctional nanocarrier for the delivery of photodynamic therapy, which, if combined with photothermal therapy, appears to be an effective therapeutic approach for cancer treatment.

The effects of oral garlic on vaginal candida colony counts: a randomised placebo controlled double-blind trial.

OBJECTIVE: Garlic is effective against Candida species in vitro, and along with other alternative therapies, is used by women with vulvovaginal candidiasis. The objective of this study was to ascertain whether oral garlic reduced vaginal candida counts during the second half of the menstrual cycle in asymptomatic women colonised with Candida species. DESIGN: A simple randomised double-blinded controlled trial. SETTING: Melbourne, Australia. SAMPLE: Sixty-three asymptomatic women who were culture-positive for Candida species at screening. METHODS: Participants were randomised to three garlic tablets or placebo orally, twice daily, for 14 days. MAIN OUTCOME MEASURES: The primary outcome was the proportion of women with colony counts of candida >100 colony-forming units per ml in any given day during the last 7 days before menstruation, defined as a 'case'. Secondary outcomes included the mean quantitative colony counts of candida over 14 days prior to menses. RESULTS: There was no evidence of a difference between the proportion of cases in the garlic and placebo groups (76 versus 90%; relative risk, RR 0.85; 95% confidence interval, 95% CI 0.67-1.08), in the mean colony counts in both groups (ratio of geometric means of candidal colony counts 0.63; 95% CI 0.39-10.03; P = 0.74), or difference in the number of women reporting abnormal vaginal symptoms during the 2 weeks before menstruation (RR 1.03; 95% CI 0.67-1.58; P = 0.91). The garlic group reported more adverse effects (83% compared 43% in the placebo group; difference in proportions 39%; 95% CI 17-%; P < 0.01). CONCLUSIONS: This study provided data for sample size calculations in future studies on the antifungal effect of garlic, but provided no evidence to inform clinical practice regarding the use of garlic in vaginal candidiasis. Further studies might investigate longer courses or topical formulations.