In Vitro Superparamagnetic Hyperthermia Employing Magnetite Gamma-Cyclodextrin Nanobioconjugates for Human Squamous Skin Carcinoma Therapy.

In vitro alternative therapy of human epidermoid squamous carcinoma (A431) by superparamagnetic hyperthermia (SPMHT) using Fe3O4 (magnetite) superparamagnetic nanoparticles (SPIONs) with an average diameter of 15.8 nm, bioconjugated with hydroxypropyl gamma-cyclodextrins (HP-γ-CDs) by means of polyacrylic acid (PAA) biopolymer, is presented in this paper. The therapy was carried out at a temperature of 43 °C for 30 min using the concentrations of Fe3O4 ferrimagnetic nanoparticles from nanobioconjugates of 1, 5, and 10 mg/mL nanoparticles in cell suspension, which were previously found by us to be non-toxic for healthy cells (cell viabilities close to 100%), according to ISO standards (cell viability must be greater than 70%). The temperature for the in vitro therapy was obtained by the safe application (without exceeding the biological limit and cellular damage) of an alternating magnetic field with a frequency of 312.4 kHz and amplitudes of 168, 208, and 370 G, depending on the concentration of the magnetic nanoparticles. The optimal concentration of magnetic nanoparticles in suspension was found experimentally. The results obtained after the treatment show its high effectiveness in destroying the A431 tumor cells, up to 83%, with the possibility of increasing even more, which demonstrates the viability of the SPMHT method with Fe3O4-PAA-(HP-γ-CDs) nanobioconjugates for human squamous cancer therapy.

Wnt Signaling Pathway Collapse upon ß-Catenin Destruction by a Novel Antimicrobial Peptide SKACP003: Unveiling the Molecular Mechanism and Genetic Activities Using Breast Cancer Cell Lines.

Despite progress in breast cancer treatment, the survival rate for patients with metastatic breast cancer remains low due to chemotherapeutic agent resistance and the lack of specificity of the current generation of cancer drugs. Our previous findings indicated that the antimicrobial peptide SKACP003 exhibited anticancer properties, particularly against the MCF-7, MDA-MB-231, and MDA-MB-453 breast cancer cell lines. However, the mechanism of SKACP003-induced cancer cell death is unknown. Here, we investigated the molecular mechanism by which SKACP003 inhibits the cell cycle, cell proliferation, and angiogenesis in breast cancer cell lines. The results revealed that all the breast cancer cell lines treated at their IC50 values significantly inhibited the replicative phase of the cell cycle. The SKACP003-induced growth inhibition induced apoptosis, as evidenced by a decrease in BCL-2 and an increase in BAX and caspase gene (Cas-3, Cas-8, and Cas-9) expression. Reduced expression of the ß-Catenin signaling pathway was associated with the SKACP003-induced apoptosis. SKACP003-treated breast cancer cells showed decreased expression of Wnt/ß-Catenin targeting genes such as C-Myc, P68, and COX-2 and significant downregulation of CDK-4 and CDK-6 genes. Furthermore, cytoplasmic ß-catenin protein levels in SKACP003-treated cell lines were significantly lower than in control cell lines. The results of the current study suggest that the newly identified antimicrobial peptide SKACP003 has great potential as a candidate for specifically targeting the ß-catenin and thus significantly reducing the progression and prognosis of breast cancer cell lines.

Pilot Intervention for Mindful Drinking and Eating for Patients on Hemodialysis with Fluid Restrictions: Lessons Learned.

Patients requiring hemodialysis would benefit from evidence-based strategies that improve adherence to fluid restrictions while concurrently improving quality of life (QOL). This pilot study examined the effect of a four-week mindful drinking and eating intervention on interdialytic weight gain and QOL in patients on hemodialysis. Using paired t tests, no significant differences from pre- to post-test were found in interdialytic weight gain, a measure of fluid restriction adherence, or QOL in either the intervention (n = 18) or wait list control (n = 19) group. However, there was positive qualitative feedback from participants in exit interviews, and there were other indications of feasibility (low drop out, engagement in at-home practice according to weekly checklists). Lessons learned from this pilot study about conducting research regarding fluid restrictions for patients on hemodialysis are presented.

Complementary and alternative medicine for treating epilepsy in China: A systematic review.

There are about 10 million people with epilepsy (PWE) in China. In addition to therapies approved by the National Medical Products Administration, the use of complementary and alternative medicine (CAM) is prevalent in Chines PWE. These CAM therapies mainly comprise traditional Chinese medicine herbs (TCMHs), acupuncture, and music. A retrospective literature search was performed to summarize the updates of CAM in China in the past ten years, and sixty-two papers were finally included. In this following review, we listed the animal and clinical studies to summarize the antiepileptic mechanisms and clinical efficacy of CAM in Chines PWE. The main mechanisms of TCMHs and acupuncture included regulation of neurotransmitters and receptors, voltage-gated ion channels modulation, expression of apoptosis-related genes, antioxidant response, and anti-inflammation. Although there were enormous clinical studies on them, the current available clinical trials were small, short-term, heterogeneous, and had a high risk of bias. With regard to music, a few studies conducted by Chinese scholars suggested that it was beneficial for PWE as an add-on therapy, which was consistent with the results of foreign studies. Further randomized clinical trials in large populations are required to prove the effectiveness and safety of CAM.

Bias and Type I error Control in Correcting Treatment Effect for Treatment Switching Using Marginal Structural Models in Phase III Oncology Trials.

This research focuses on the bias and type I error control issues when the marginal structural models (MSMs) are applied to evaluate the causal survival benefits of active intervention versus control in randomized clinical trials (RCTs) with treatment switching after disease progression. When MSMs are applied in the RCT setting, the question of interest, model specifications, strategies for type I error control, bias reduction, etc. differ somewhat from those for observational studies. This manuscript discusses the approaches used to accommodate these differences. Through Monte Carlo simulations and a case study, our research demonstrates that, with sufficient attention paid to issues applicable to RCTs in particular, MSMs may perform better than the inverse probability of censoring weighting (IPCW) method in analyzing the survival endpoint in RCTs with treatment switching because more information is used by the MSM.

Platelet-rich plasma in animal reproductive medicine: Prospective and applications.

Platelet-rich plasma (PRP) is the fraction of the plasma enriched with a platelet level above baseline, and it plays an essential role in tissue regeneration. The attention to PRP as unconventional therapy has increased during the past two decades. In animals, applications of PRP showed various degrees of success in a wide range of medical applications, from musculoskeletal injuries to ovarian insufficiency. Therapeutic applications with PRP in farm animals are still scarce, but the promising results offered by several studies are expected to trigger more interest in its application by both veterinarians and farmers. In this review, we highlight some efforts made in the field of animal reproduction regarding the use of PRP to potentiate the ovarian hypofunction, treat endometritis, improve the follicular development, oocyte competence and uterine environment for embryo implantation as well as restore testicular and erectile function in male, and as a treatment for mastitis.

When time does not heal all wounds-the use of medical grade honey in wound healing: a case series.

OBJECTIVE: Hard-to-heal wounds can be caused by persistent infections or an excess of inflammatory cytokines, proteases and oxidants, and can severely impact the quality of life (QoL) of patients. Due to the paucity of effective treatments and increased resistance to antibiotics, new and improved therapies are required to resolve infections and to simultaneously enhance the healing trajectory. Medical grade honey (MGH) may be a novel and effective treatment approach. METHODS: In this case series, we have described six cases of hard-to-heal wounds, and discussed the effects of MGH on infection, wound healing and factors influencing patient QoL (pain, odour and exudate). In all cases, the wounds had persisted for a long period, and previous treatments had been ineffective. Most of the patients had comorbidities, and the majority of the wounds were contaminated with (multiresistant) bacteria, both of which contributed to non-healing. All wounds were treated with L-Mesitran (MGH-based wound care products, Triticum Exploitatie BV, the Netherlands) either as monotherapy or as a complementary therapy. RESULTS: Hard-to-heal wounds started healing, infection was controlled and QoL was strongly improved (malodour, exudate levels and pain swiftly decreased) after the application of the MGH. All wounds healed relatively quickly, considering the severity of the wounds and general health of the patients. CONCLUSION: In this study, MGH was a useful alternative or complementary therapy to antibiotics and expedited the healing of hard-to-heal wounds.

[Treatment of bone and periprosthetic infections with bacteriophages : A systematic review]. / Behandlung von Knochen- und Protheseninfektionen mit Bakteriophagen : Ein systematisches Review.

BACKGROUND: The treatment of bone and prosthesis infections remains difficult despite modern treatment concepts. Further tools for the improvement of treatment outcome are desirable. Preclinical studies provide promising evidence of the efficacy of bacteriophages for the treatment of bone and joint infections. OBJECTIVES: The present work provides a systematic review of the clinical application of bacteriophages for the treatment of bone and joint infections. MATERIALS AND METHODS: A systematic search was performed in PubMed to identify primary clinical data on the use of phage therapy in patients with bone and joint infection. RESULTS: Eight case reports and three case series were included in the study. Indications for phage therapy were periprosthetic joint infection (n = 12, 52.2%), fracture-related infection (n = 9, 39.1%), osteomyelitis (n = 1, 4.4%) and sacroiliac joint infection after cement augmentation of a metastasis (n = 1, 4.4%). Interventions were heterogeneous; phages were administered intravenously, injected intraoperatively into the joint, applied locally intraoperatively, or administered via drains. In combination with antibiotic therapy, complete infection eradication was achieved in 18 patients (78.3%). No side effects were reported in 91.3% of patients. CONCLUSION: Bacteriophages represent a promising treatment option for bone and prosthesis infections in combination with antibiotic therapy. Future clinical trials with a higher level of evidence are required for the successful translation of bacteriophage therapy into clinical practice.

Preliminary cost variance modeling to compare autologous intraovarian platelet-rich plasma vs. standard hormone replacement therapy for menopause management.

BACKGROUND: Menopause symptoms and hormone replacement therapy (HRT) are among the most common reasons patients seek gynecological advice. Although at least half of all women in developed countries will use HRT during their lifetime, the treatment is not without risk and guidance on HRT is mixed. Greater awareness of HRT risks from extended use has piqued interest in safer options. Menopause reversal with autologous ovarian platelet-rich plasma (OPRP) has brought this restorative approach forward for consideration, but appropriateness and cost-effectiveness require examination. METHODS: HRT and OPRP data from USA were projected to compare cumulative 1yr patient costs using stochastic Monte Carlo modeling. RESULTS: Mean ± SD cost-to-patient for HRT including initial consult plus pharmacy refills was estimated at about $576 ± 246/yr. While OPRP included no pharmacy component, an estimated 4 visits over 1yr for OPRP maintenance entailed ultrasound, phlebotomy/sample processing, surgery equipment, and incubation/laboratory expense, yielding mean ± SD cost for OPRP at $8,710 ± 4,911/yr ( P < 0.0001 vs. HRT, by T-test). Upper-bound estimates for annual HRT and OPRP costs were $1,341 and $22,232, respectively. CONCLUSIONS: While HRT and OPRP may have similar efficacy and safety for menopause therapy, they diverge sharply in cost-effectiveness. Most patients would likely find OPRP too complex, invasive, and expensive to be competitive vs. HRT. Although OPRP is an interesting and cautiously useful technique for selected menopause patients reluctant to use HRT, repurposing this infertility treatment for wider use appears inefficient compared to standard HRT options that are currently marketed.

Exploring the effect of neurofeedback on postcancer cognitive impairment and fatigue: A pilot feasibility study.

Purpose: Postcancer cognitive impairment (PCCI) and fatigue are adverse effects that often persist following cancer treatment, and impact quality of life. The study purpose was to evaluate feasibility and effect of neurofeedback on cognitive functioning and fatigue in cancer survivors. Specifically, we aimed to test feasibility of recruitment strategies and our study protocol including outcome measures. Design: This pilot feasibility study used a 10-week wait-list design. Participants served as their own controls and received neurofeedback training twice a week for 10 weeks. Participants: The sample consisted of breast cancer survivors from Kingston, Ontario (n = 16). Methods: Outcomes were assessed using validated, self-report scales and neuropsychological tests before, during, and after neurofeedback. Findings: The neurofeedback protocol was feasible and resulted in significant decreases in perceived cognitive deficits, fatigue, sleep, and psychological symptoms. Implications for psychosocial providers: Neurofeedback may be an effective, non-invasive complementary therapy for PCCI in breast cancer survivors.

Update on Candida krusei, a potential multidrug-resistant pathogen.

Although Candida albicans remains the main cause of candidiasis, in recent years a significant number of infections has been attributed to non-albicans Candida (NAC) species, including Candida krusei. This epidemiological change can be partly explained by the increased resistance of NAC species to antifungal drugs. C. krusei is a diploid, dimorphic ascomycetous yeast that inhabits the mucosal membrane of healthy individuals. However, this yeast can cause life-threatening infections in immunocompromised patients, with hematologic malignancy patients and those using prolonged azole prophylaxis being at higher risk. Fungal infections are usually treated with five major classes of antifungal agents which include azoles, echinocandins, polyenes, allylamines, and nucleoside analogues. Fluconazole, an azole, is the most commonly used antifungal drug due to its low host toxicity, high water solubility, and high bioavailability. However, C. krusei possesses intrinsic resistance to this drug while also rapidly developing acquired resistance to other antifungal drugs. The mechanisms of antifungal resistance of this yeast involve the alteration and overexpression of drug target, reduction in intracellular drug concentration and development of a bypass pathway. Antifungal resistance menace coupled with the paucity of the antifungal arsenal as well as challenges involved in antifungal drug development, partly due to the eukaryotic nature of both fungi and humans, have left researchers to exploit alternative therapies. Here we briefly review our current knowledge of the biology, pathophysiology and epidemiology of a potential multidrug-resistant fungal pathogen, C. krusei, while also discussing the mechanisms of drug resistance of Candida species and alternative therapeutic approaches.

The Effectiveness of Nasal Airway Stent Therapy for the Treatment of Mild-to-Moderate Obstructive Sleep Apnea Syndrome.

BACKGROUND: Patients with obstructive sleep apnea syndrome (OSAS) experience excessive daytime sleepiness and insomnia and they are at risk of developing cardiovascular disease and stroke. Continuous positive airway pressure therapy could improve symptoms and decrease these risks; however, adherence is problematic. Although the oral appliance is another therapeutic option, patient satisfaction is limited and the effect of the nasal airway stent - a new device - remains unclear. OBJECTIVES: The aim of this study was to evaluate the effect of NAS therapy in patients with mild-to-moderate OSAS in a prospective, single-arm, interventional pilot study. METHOD: Patients with mild/moderate sleep apnea (n = 71; Apnea-Hypopnea Index [AHI], 5-20 events/h on polysomnography) were recruited. Sleep-associated events were measured using a portable device (WatchPAT200) pre- and immediately post-treatment and at 1 month follow-up. AHI (including supine and non-supine AHI), Oxygen Desaturation Index (ODI), Respiratory Disturbance Index (RDI), percutaneous oxygen saturation, heart rate, and snore volume were evaluated. Symptoms were assessed using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Hospital Anxiety and Depression Scale. RESULTS: NAS use significantly improved AHI, supine AHI, RD, ODI, and snore volume compared to pre-intervention (r = 0.44, 0.48, 0.3, 0.42, and 0.34; p < 0.001, p < 0.001, p = 0.011, p < 0.001, and p = 0.048, respectively). Additionally, 25 and 10% of patients showed complete and partial response for AHI, respectively; these improvements remained significant 1 month later. Pittsburgh Sleep Quality Index scores improved from 6.0 to 5.3 (r = 0.46, p = 0.022). CONCLUSIONS: NAS therapy reduced severity and snoring in patients with mild-to-moderate OSAS. Approximately 30% of patients did not tolerate NAS due to side effects.

Acupuncture for the Management of Low Back Pain.

PURPOSE OF REVIEW: This evidence-based systematic review will focus on the use of acupuncture and its role in the treatment of low back pain to help better guide physicians in their practice. It will cover the background and the burden of low back pain and present the current options for treatment and weigh the evidence that is available to support acupuncture as a treatment modality for low back pain. RECENT FINDINGS: Low back pain (LBP), defined as a disorder of the lumbosacral spine and categorized as acute, subacute, or chronic, can be a debilitating condition for many patients. Chronic LBP is more typically defined by its chronicity with pain persisting > 12 weeks in duration. Conventional treatment for chronic LBP includes both pharmacologic and non-pharmacologic options. First-line pharmacologic therapy involves the use of NSAIDs, then SNRI/TCA/skeletal muscle relaxants, and antiepileptics. Surgery is usually not recommended for chronic non-specific LBP patients. According to the 2016 CDC Guidelines for Prescribing Opioids for Chronic Pain and the 2017 American College of Physicians (ACP) clinical practice guidelines for chronic pain, non-pharmacologic interventions, acupuncture can be a first-line treatment for patients suffering from chronic low back pain. Many studies have been done, and most show promising results for acupuncture as an alternative treatment for low back pain. Due to non-standardized methods for acupuncture with many variations, standardization remains a challenge.

Is the use of alternative therapy in children just another form of medicalisation? A prospective study.

AIM: The use of complementary and alternative medicines (CAM) seems widespread in adults and children, despite the conflicting evidence regarding its effectiveness and safety. This study aims to investigate the prevalence of the use of CAM in a population of Italian children. METHODS: This is a prospective observational study conducted in 4 family paediatric clinics, in Friuli Venezia Giulia, Italy, from February to June 2019. Children were enrolled after being visited. The use of CAM and essential therapies (ET) in the previous year was investigated with an anonymous questionnaire. The demographic characteristics of children and families were also collected. RESULTS: Six hundred children were enrolled, mean age 5.8 years, 50% females. In the previous year, 358 (60%) children used both essential therapies and CAM, 209 children (35%) only essential therapies, 25 (4%) only CAM, and 8 (1%) no therapy. CAM was more frequently used in children whose parents have a higher educational level and come from high-income countries (P < .0001). Non-vaccinated children received more CAM than vaccinated ones (P < .003). CONCLUSION: In our population, more than 60% of children receive CAM. The use of this medical approach seems strictly related to the social and cultural status of families.

Efficacy of Ginger in Preventing Postoperative Nausea and Vomiting: A Systematic Review and Meta-Analysis.

PURPOSE: We aimed to synthesize the published evidence to evaluate the preventive efficacy of ginger on postoperative nausea and vomiting (PONV). DESIGN: A systematic review and meta-analysis were conducted in this study. METHODS: PubMed, EMBASE, Cochrane Library, and CINAHL were systematically searched from their outset to October 2020, without language limitation. Randomized controlled trials (RCTs) comparing the effects of ginger and prophylactic antiemetics or placebo on PONV were included. Data were analyzed by the fixed effects model or random effects models regarding the results of heterogeneity. FINDINGS: A total of 14 studies involving 1417 participants were included. Compared with placebo, the ginger group had significantly lower nausea severity (MD = -0.71, 95% CI = -1.37 to -0.06, p = 0.03) and lower proportion of rescue antiemetic use (RR = 0.71, 95% CI = 0.62-0.82, p < 0.001; RR = 0.71, 95% CI = 0.56-0.91, p < 0.001). The ginger group had significantly lower incidence of nausea and vomiting over 6 h after operation (RR = 0.68, 95% CI = 0.55-0.85, p < 0.001; RR = 0.78, 95% CI = 0.42-1.44, p = 0.43) compared with placebo. When compared with the prophylactic antiemetic group, the ginger group had significantly lower incidence of nausea (RR = 0.75, 95% CI = 0.56-0.99, p = 0.04), but no significant differences in the incidence of vomiting and proportion of rescue antiemetic use were found. CONCLUSIONS: Ginger was effective for the prevention of PONV. More RCTs comparing ginger and other prophylactic antiemetics are needed to evaluate whether ginger could replace the traditional prophylactic antiemetics. CLINICAL RELEVANCE: This study's results could be used as an evidence for all patients following surgery who are at risk of PONV without allergy to ginger.

Revisiting Therapeutic Strategies for H. pylori Treatment in the Context of Antibiotic Resistance: Focus on Alternative and Complementary Therapies.

The prevalence of Helicobacter pylori infection remains significant worldwide and it depends on many factors: gender, age, socio-economic status, geographic area, diet, and lifestyle. All successful infectious diseases treatments use antibiotic-susceptibility testing, but this strategy is not currently practical for H. pylori and the usual cure rates of H. pylori are lower than other bacterial infections. Actually, there is no treatment that ensures complete eradication of this pathogen. In the context of an alarming increase in resistance to antibiotics (especially to clarithromycin and metronidazole), alternative and complementary options and strategies are taken into consideration. As the success of antibacterial therapy depends not only on the susceptibility to given drugs, but also on the specific doses, formulations, use of adjuvants, treatment duration, and reinfection rates, this review discusses the current therapies for H. pylori treatment along with their advantages and limitations. As an alternative option, this work offers an extensively referenced approach on natural medicines against H. pylori, including the significance of nanotechnology in developing new strategies for treatment of H. pylori infection.

In Silico Screening and In Vitro Assessment of Natural Products with Anti-Virulence Activity against Helicobacter pylori.

Helicobacter pylori is one of the most frequent human pathogens and a leading etiological agent of various gastric diseases. As stringent response, coordinated by a SpoT protein, seems to be crucial for the survivability of H. pylori, the main goal of this article was to use in silico computational studies to find phytochemical compounds capable of binding to the active site of SpoT from H. pylori and confirm the ability of the most active candidates to interfere with the virulence of this bacterium through in vitro experiments. From 791 natural substances submitted for the virtual screening procedure, 10 were chosen and followed for further in vitro examinations. Among these, dioscin showed the most interesting parameters (the lowest MIC, the highest anti-biofilm activity in static conditions, and a relatively low stimulation of morphological transition into coccoids). Therefore, in the last part, we extended the research with a number of further experiments and observed the ability of dioscin to significantly reduce the formation of H. pylori biofilm under Bioflux-generated flow conditions and its capacity for additive enhancement of the antibacterial activity of all three commonly used antibiotics (clarithromycin, metronidazole, and levofloxacin). Based on these results, we suggest that dioscin may be an interesting candidate for new therapies targeting H. pylori survivability and virulence.

Daily consumption of a homeopathic product decreases intestinal damage and stool bacterial counts in mice challenged with Escherichia coli.

Escherichia coli is a bacterium normally found in the gastrointestinal tract of domestic animals that can usually control the infection. Nevertheless, some factors (high exposure, stress conditions, animal category, among others) can favor the exacerbation of E. coli infection and cause of disease. Because it is a zoonotic bacterium, it is important to control the infection, avoiding contamination of home interiors in the case of pets. There are various forms of treatment for E. coli; nevertheless, there are few options for prevention. In the present study, we evaluated homeopathy. Thus, the objective of this study was to determine whether administration of a prophylactic homeopathic in water would minimize the negative effects of E. coli infection, as well as reducing bacterial counts in the feces of a experimental model. Forty mice were divided into four experimental groups (n = 10/group). Groups NC (negative control) and PC (positive control) were not treated; in group T1, the animals received 0.002 mL/day/animal of the homeopathic in water, and animals in group T2 0.004 mL/day/animal. The experiment lasted 54 days, and on the 31st day, mice of T1, T2 and PC groups were infected orally a 0.2 mL inoculum of 1.5 × 108 CFU of E. coli. Euthanasia and sample collection were performed on the 40th and 54th days of the experiment (n = 5/group/time point). Blood, liver, spleen, intestine, and feces samples were collected from the final portion of the intestine. There was no significant difference in animal weight between groups at the end of the experiment. Neutrophil count was lower in PC group animals on day 40, while on day 54, the counts were lower in T2 and PC. Lymphocyte counts were lower only in the PC group than in the NC group on day 54. Globulins were lower in the NC and PC groups than in T1 and T2 on day 40, remaining lower the PC group and higher in T1 on day 54; levels of immunoglobulin IgG and IgM were higher in groups T1 and T2, which differed from PC and NC. TNF-α levels were higher in the T1 and T2 groups at 40 and 54 days. INF-γ levels were higher in T1, T2, and PC compared to NC on day 40, remaining higher than NC in groups T1 and T2 on day 54. Total bacterial count, total coliforms and E. coli counts were lower in group T1 and higher in NC and PC on days 40 and 54, when they were lower for T1 and T2. Histologically, no lesions were observed in extra-intestinal tissues; however the height of intestinal crypts in the PC group was smaller than the others on day 40. On day 54, villi and crypts of all infected groups were larger in T1 and T2 than in NC; sizes in the PC group were higher than those of all other groups. These data suggest that the homeopathic agent in the drinking water improved health of the mice.

The modulatory effect of triclosan on the reversion of the activated phenotype of LX-2 hepatic stellate cells.

Hepatic diseases leading to fibrosis affect millions of individuals worldwide and are a major public health challenge. Although, there have been many advances in understanding hepatic fibrogenesis, an effective therapy remains elusive. Studies focus primarily on activation of the hepatic stellate cells (HSCs), the principal fibrogenic cells in the liver; however, fewer numbers of studies have examined molecular mechanisms that deactivate HSC, controlling the profibrogenic phenotype. In the present study, we evaluated cellular and molecular actions of the chemical triclosan (TCS) in reverting activated HSCs to a quiesced phenotype. We demonstrated that the inhibition of the enzyme fatty acid synthase by TCS in activated HSCs promotes survival of the cells and triggers cellular and molecular changes that promote cellular phenotypic reversion, offering potentially new therapeutic directions.

Staphylococcus aureus persistence properties associated with bovine mastitis and alternative therapeutic modalities.

Staphylococcus aureus is an important agent of contagious bovine intramammary infections in dairy cattle. Its ability to persist inside the udder is based on the presence of important mechanisms such as its ability to form biofilms, polysaccharide capsules small colony variants, and their ability to invade professional and nonprofessional cells, which will protect S. aureus from the innate and adaptive immune response of the cow, and from antibiotics that are no longer considered to be sufficient against S. aureus bovine mastitis. In this review, we present the recent research outlining S. aureus persistence properties inside the mammary gland, including its regulation mechanisms, and we highlight alternative therapeutic strategies that were tested against S. aureus isolated from bovine mastitis such as the use of probiotic bacteria, bacteriocins and bacteriophages. Overall, the persistence of S. aureus inside the mammary gland remains a pressing veterinary problem. A thorough understanding of staphylococcal persistence mechanisms will elucidate novel ways that can help in the identification of novel treatments.