In vitro antimicrobial effect and in vivo preventive and therapeutic effects of partially purified lantibiotic lacticin NK34 against infection by Staphylococcus species isolated from bovine mastitis

AbstractIntroductionBovine mastitis is an inflammatory disease of the udder that causes important economic losses in the animal breeding and dairy product industries. Nowadays, the conventional livestock antibiotic treatments are slowly being replaced by alternative treatments. In this context, the main aim of this study was to evaluate the efficacy of natural products in alternative treatment of bovine mastitis.Material and MethodsTwo natural formulations with previously suggested in vitro antimicrobial effect were tested in vivo on mastitic cows. Animals with a positive diagnosis for mastitis (n = 20) were divided into three treatment groups: two groups (n = 8) were administered formulations of propolis, alcoholic extracts of Brewers Gold and Perle hops, plum lichen, common mallow, marigold, absinthe wormwood, black poplar buds, lemon balm, and essential oils of oregano, lavender, and rosemary designated R4 and R7 (differing only in the latter being more concentrated) and one group (n = 4) a conventional antibiotic mixture. In vivo efficacy of treatments was evaluated by somatic cell and standard plate counts, the treatment being considered efficacious when both parameters were under the maximum limit.ResultsR7 was effective in the most cases, being therapeutically bactericidal in six out of eight cows, while R4 gave good results in three out of eight cows, and conventional antibiotics cured one out of four.ConclusionThese results suggest the possible therapeutic potential of these natural products in bovine mastitis.

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Clinical Trials in Thrombosis: Secondary Prevention of Myocardial Infarction

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647910 ◽

1976 ◽

Vol 35 (01) ◽

pp. 049-056 ◽

Cited By ~ 4

Author(s):

Christian R Klimt ◽

P. H Doub ◽

Nancy H Doub

Keyword(s):

Myocardial Infarction ◽

Secondary Prevention ◽

Case Control ◽

Therapeutic Effects ◽

Case Control Studies ◽

Definitive Answer ◽

Inhibition Of Platelet Aggregation ◽

Prospective Trials

SummaryNumerous in vivo and in vitro experiments, investigating the inhibition of platelet aggregation and the prevention of experimentally-induced thrombosis, suggest that anti-platelet drugs, such as aspirin or the combination of aspirin and dipyridamole or sulfinpyrazone, may be effective anti-thrombotic agents in man. Since 1971, seven randomized prospective trials and two case-control studies have been referenced in the literature or are currently being conducted, which evaluate the effects of aspirin, sulfinpyrazone, or dipyridamole in combination with aspirin in the secondary prevention of myocardial infarction. A critical review of these trials indicates a range of evidence from no difference to a favorable trend that antiplatelet drugs may serve as anti-thrombotic agents in man. To date, a definitive answer concerning the therapeutic effects of these drugs in the secondary prevention of coronary heart disease is not available.

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Therapeutic effects of sesamolin on leukemia induced by WEHI-3B in model mice

Applied Biological Chemistry ◽

10.1186/s13765-021-00616-3 ◽

2021 ◽

Vol 64 (1) ◽

Author(s):

Senthil Nagarajan ◽

Jae Kwon Lee

Keyword(s):

Nk Cell ◽

Neoplastic Cell ◽

Positive Control ◽

Cytolytic Activity ◽

Leukemic Cells ◽

Therapeutic Effects ◽

Control Drug ◽

Lysis Activity

AbstractSesamolin is one of the lignans derived from sesame oil. It has demonstrated significant antioxidant, anti-aging, and anti-mutagenic properties. It also reportedly augments natural killer (NK) cell lysis activity. We previously reported that sesamolin also exerts anticancer effects in vitro and induces enhanced NK cell cytolytic activity against tumor cells. Herein, we aimed to determine the mechanism by which sesamolin prevents and retards tumorigenesis in BALB/c mouse models of leukemia induced by murine (BALB/c) myelomonocytic leukemia WEHI-3B cells. Banded neutrophils, myeloblasts, and monocytic leukemic cells were more abundant in the leukemia model than in normal mice. Sesamolin decreased the number of leukemic cells by almost 60% in the leukemia model mice in vivo; additionally, sesamolin and the positive control drug, vinblastine, similarly hindered neoplastic cell proliferation. Spleen samples were ~ 4.5-fold heavier in leukemic mice than those obtained from normal mice, whereas spleen samples obtained from leukemic mice treated with sesamolin had a similar weight to those of normal mice. Moreover, sesamolin induced a twofold increase in the cytotoxic activity of leukemic mouse NK cells against WEHI-3B cells. These results indicated that sesamolin exerts anti-leukemic effects in vivo.

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The Therapeutic Effect of Extracellular Vesicles on Asthma in Pre-Clinical Models: A Systematic Review Protocol

Journal of Respiration ◽

10.3390/jor1010009 ◽

2021 ◽

Vol 1 (1) ◽

pp. 84-95

Author(s):

Patience O. Obi ◽

Jennifer E. Kent ◽

Maya M. Jeyaraman ◽

Nicole Askin ◽

Taiana M. Pierdoná ◽

...

Keyword(s):

Systematic Review ◽

Extracellular Vesicles ◽

Current Knowledge ◽

Grey Literature ◽

Specific Treatment ◽

Therapeutic Effects ◽

Management Options ◽

Paracrine Signalling

Asthma is the most common pediatric disease, characterized by chronic airway inflammation and airway hyperresponsiveness. There are several management options for asthma, but no specific treatment. Extracellular vesicles (EVs) are powerful cellular mediators of endocrine, autocrine and paracrine signalling, and can modulate biophysiological function in vitro and in vivo. A thorough investigation of therapeutic effects of EVs in asthma has not been conducted. Therefore, this systematic review is designed to synthesize recent literature on the therapeutic effects of EVs on physiological and biological outcomes of asthma in pre-clinical studies. An electronic search of Web of Science, EMBASE, MEDLINE, and Scopus will be conducted on manuscripts published in the last five years that adhere to standardized guidelines for EV research. Grey literature will also be included. Two reviewers will independently screen the selected studies for title and abstract, and full text based on the eligibility criteria. Data will be extracted, narratively synthesized and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will summarize the current knowledge from preclinical studies investigating the therapeutic effects of EVs on asthma. The results will delineate whether EVs can mitigate biological hallmarks of asthma, and if so, describe the underlying mechanisms involved in the process. This insight is crucial for identifying key pathways that can be targeted to alleviate the burden of asthma. The data will also reveal the origin, dosage and biophysical characteristics of beneficial EVs. Overall, our results will provide a scaffold for future intervention and translational studies on asthma treatment.

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A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway

Cancer Cell International ◽

10.1186/s12935-021-01973-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xuejie Gao ◽

Bo Li ◽

Anqi Ye ◽

Houcai Wang ◽

Yongsheng Xie ◽

...

Keyword(s):

Mouse Model ◽

Tumor Burden ◽

High Rate ◽

Cell Counting ◽

Tumor Xenograft ◽

Luciferase Reporter ◽

Therapeutic Effects ◽

Xenograft Mouse Model

Abstract Background Multiple myeloma (MM) is a highly aggressive and incurable clonal plasma cell disease with a high rate of recurrence. Thus, the development of new therapies is urgently needed. DCZ0805, a novel compound synthesized from osalmide and pterostilbene, has few observed side effects. In the current study, we intend to investigate the therapeutic effects of DCZ0805 in MM cells and elucidate the molecular mechanism underlying its anti-myeloma activity. Methods We used the Cell Counting Kit-8 assay, immunofluorescence staining, cell cycle assessment, apoptosis assay, western blot analysis, dual-luciferase reporter assay and a tumor xenograft mouse model to investigate the effect of DCZ0805 treatment both in vivo and in vitro. Results The results showed that DCZ0805 treatment arrested the cell at the G0/G1 phase and suppressed MM cells survival by inducing apoptosis via extrinsic and intrinsic pathways. DCZ0805 suppressed the NF-κB signaling pathway activation, which may have contributed to the inhibition of cell proliferation. DCZ0805 treatment remarkably reduced the tumor burden in the immunocompromised xenograft mouse model, with no obvious toxicity observed. Conclusion The findings of this study indicate that DCZ0805 can serve as a novel therapeutic agent for the treatment of MM.

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Therapeutic effects of EGF-modified curcumin/chitosan nano-spray on wound healing

Regenerative Biomaterials ◽

10.1093/rb/rbab009 ◽

2021 ◽

Vol 8 (2) ◽

Author(s):

Yue Li ◽

QingQing Leng ◽

XianLun Pang ◽

Huan Shi ◽

YanLin Liu ◽

...

Keyword(s):

Drug Delivery ◽

Wound Healing ◽

Chitosan Nanoparticles ◽

Skin Lesions ◽

In Vitro Assays ◽

Therapeutic Effects ◽

Skin Defects ◽

Post Operation

Abstract Dermal injury, including trauma, surgical incisions, and burns, remain the most prevalent socio-economical health care issue in the clinic. Nanomedicine represents a reliable administration strategy that can promote the healing of skin lesions, but the lack of effective drug delivery methods can limit its effectiveness. In this study, we developed a novel nano-drug delivery system to treat skin defects through spraying. We prepared curcumin-loaded chitosan nanoparticles modified with epidermal growth factor (EGF) to develop an aqueous EGF-modified spray (EGF@CCN) for the treatment of dermal wounds. In vitro assays showed that the EGF@CCN displayed low cytotoxicity, and that curcumin was continuously and slowly released from the EGF@CCN. In vivo efficacy on wound healing was then evaluated using full-thickness dermal defect models in Wistar rats, showing that the EGF@CCN had significant advantages in promoting wound healing. On day 12 post-operation, skin defects in the rats of the EGF@CCN group were almost completely restored. These effects were related to the activity of curcumin and EGF on skin healing, and the high compatibility of the nano formulation. We therefore conclude that the prepared nano-scaled EGF@CCN spray represents a promising strategy for the treatment of dermal wounds.

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Stem cells and exosomes: promising candidates for necrotizing enterocolitis therapy

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02389-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ruijie Zeng ◽

Jinghua Wang ◽

Zewei Zhuo ◽

Yujun Luo ◽

Weihong Sha ◽

...

Keyword(s):

Stem Cells ◽

Necrotizing Enterocolitis ◽

Therapeutic Effects ◽

Beneficial Effects ◽

Pediatric Diseases ◽

Gastrointestinal Conditions ◽

Different Types ◽

Novel Therapeutic Strategies

AbstractNecrotizing enterocolitis (NEC) is a devastating disease predominately affecting neonates. Despite therapeutic advances, NEC remains the leading cause of mortality due to gastrointestinal conditions in neonates. Stem cells have been exploited in various diseases, and the application of different types of stem cells in the NEC therapy is explored in the past decade. However, stem cell transplantation possesses several deficiencies, and exosomes are considered potent alternatives. Exosomes, especially those derived from stem cells and breast milk, demonstrate beneficial effects for NEC both in vivo and in vitro and emerge as promising options for clinical practice. In this review, the function and therapeutic effects of stem cells and exosomes for NEC are investigated and summarized, which provide insights for the development and application of novel therapeutic strategies in pediatric diseases. Further elucidation of mechanisms, improvement in preparation, bioengineering, and administration, as well as rigorous clinical trials are warranted.

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Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

Molecules ◽

10.3390/molecules26092506 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2506

Author(s):

Wamidh H. Talib ◽

Ahmad Riyad Alsayed ◽

Alaa Abuawad ◽

Safa Daoud ◽

Asma Ismail Mahmod

Keyword(s):

Clinical Trials ◽

Current Knowledge ◽

Biological Activities ◽

Experimental Studies ◽

Therapeutic Effects ◽

Cell Proliferation Inhibition ◽

Different Types ◽

Solid Foundation

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.

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Strong Antimicrobial and Healing Effects of Beta-Acids from Hops in Methicillin-Resistant Staphylococcus aureus-Infected External Wounds In Vivo

Antibiotics ◽

10.3390/antibiotics10060708 ◽

2021 ◽

Vol 10 (6) ◽

pp. 708

Author(s):

Radek Sleha ◽

Vera Radochova ◽

Jiri Malis ◽

Alexander Mikyska ◽

Milan Houska ◽

...

Keyword(s):

Wound Healing ◽

Porcine Model ◽

Therapeutic Effects ◽

Methicillin Resistant ◽

Antimicrobial Effects ◽

Therapeutic Modalities ◽

Positive Effects ◽

Inflammatory Parameters

Staphylococcus (S.) aureus is an important causative agent of wound infections with increasing incidence in the past decades. Specifically, the emergence of methicillin-resistant S. aureus (MRSA) causes serious problems, especially in nosocomial infections. Therefore, there is an urgent need to develop of alternative or supportive antimicrobial therapeutic modalities to meet these challenges. Purified compounds from hops have previously shown promising antimicrobial effects against MRSA isolates in vitro. In this study, purified beta-acids from hops were tested for their potential antimicrobial and healing properties using a porcine model of wounds infected by MRSA. The results show highly significant antimicrobial effects of the active substance in both the powder and Ambiderman-based application forms compared to both no-treatment control and treatment with Framycoin. Moreover, the macroscopic evaluation of the wounds during the treatment using the standardized Wound Healing Continuum indicated positive effects of the beta-acids on the overall wound healing. This is further supported by the microscopic data, which showed a clear improvement of the inflammatory parameters in the wounds treated by beta-acids. Thus, using the porcine model, we demonstrate significant therapeutic effects of hops compounds in the management of wounds infected by MRSA. Beta-acids from hops, therefore, represent a suitable candidate for the treatment of non-responsive nosocomial tissue infections by MRSA.

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Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

Molecular Medicine ◽

10.1186/s10020-021-00332-0 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Jian-Ping Zhang ◽

Wei-Jing Zhang ◽

Miao Yang ◽

Hua Fang

Keyword(s):

Cell Apoptosis ◽

Ischemia Reperfusion Injury ◽

Glycogen Synthase ◽

Ischemia Reperfusion ◽

Inflammatory Factors ◽

Therapeutic Effects ◽

Protective Effects ◽

Loss Of Function

Abstract Background Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β). Methods C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured. Results Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression. Conclusion Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

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