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Impaired CTLA-4 responses in COPD are associated with systemic inflammation

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Cellular & Molecular Immunology 2014年第6期11卷 606-608页

作者： dino BA Tan Sonia Fernandez PatriciaPrice Martyn A French Philip j Thompson Yuben P Moodley Centre for Asthma Allergy and Respiratory Research Lung Institute of Western Australia Nedlands Australia School of Medicine and Pharmacology Nedlands Australia School of Pathology and Laboratory Medicine University of Western Australia Nedlands Australia Department of Clinical Immunology Perth Australia Department of Respiratory and Sleep Medicine Royal Perth Hospital Perth Australia

Systemic inflammation is a feature of chronic obstructive pulmo- nary disease （COPD）. Defects in T cell-mediated anti-inflamma- tory pathways such as cytotoxic T lymphocyte antigen-4 （CTLA- 4） may promote damaging inflammation. This study provides novel data implicating the impaired induction of an anti-inflam- matory molecule, CTLA-4 in the elevated inflammation observed in COPD patients. Low induction of CTLA-4 in COPD patients paralleled increased markers of systemic inflammation ex vivo and increased T-cell responses to a bacterial superantigen, staphylo- coccal enterotoxin-B （SEB） in vitro. This mechanism may explain the increased inflammation in COPD patients.

关键词： Impaired responses associated

In silico analysis of RNA and small RNA sequencing data from human BM-MSCs and differentiated osteocytes, chondrocytes and tenocytes

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Engineered Regeneration 2021年第1期2卷 19-30页

作者： Srinivas V.Koduru Irina A.Elcheva Ashley N.Leberfinger dino j.Ravnic Irvin S.Zubar Plastic Surgery Research Laboratory Penn State College of Medicine500 University DriveHersheyPA 17033-0850United States Department of Surgery Penn State Health Milton S.Hershey Medical CenterHersheyPAUnited States Department of Cellular and Molecular Physiology Penn State College of MedicineHersheyPAUnited States Division of Pediatric Hematology/Oncology Department of PediatricsPenn State College of MedicineHersheyPAUnited States

Background:Adult stem cells have a remarkable capacity of differentiating into various cell types necessary for tissue and organ *** studies have focused on the differentiation potential of mesenchymal stem cells(MSCs),however little is known about the molecular characteristics of MSCs and their progenies obtained from donors of different *** this study,we analyzed publicly available sequencing data obtained from young(~22-year-old,n=8)and older(~65.5-year-old,n=8)donors of MSCs and their differentiated counterparts:osteocytes,chondrocytes and *** raw mRNA and small RNA(non-coding RNA)sequencing data was downloaded from NIH BioProjects and systematically analyzed in order to identify uniquely expressed genes in MSC-derived osteocytes,chondrocytes and tenocytes of younger and older ***:We identified many commonly up-and downregulated genes are similar in both ***,the young group displayed a greater variety of differentially expressed genes in all analyzed MSC-derived *** discrepancy in gene expression profiles between younger and older groups may indicate a greater differentiation potential of MSCs isolated from younger *** and mRNA integrated analysis showed key miRNAs that regulate mRNAs in both groups from all differentiated ***:Our analysis provides additional information to previously reported data for identification of MSC markers of plasticity and *** addition,our data may shed light upon the molecular mechanisms of age-associated musculoskeletal diseases caused by a decreased capacity of MSCs to regenerate the locomotor system in elderly people.

关键词： BM-MSCs Osteocytes Chondrocytes Tenocytes Small RNA miRNA-mRNA

Genetically Targeted Fractionated Chemotherapy

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journal of Cancer Therapy 2015年第2期6卷 182-198页

作者： Aaron j. Smith john Oertle dino Prato Envita Scottsdale USA

Complex and late stage cancer patients are in need of novel methods of selecting and administering chemotherapy particularly for those patients who are refractory to current treatment methods. The use of biomarkers to enhance decision making with regard to the molecular profile of a person’s cancer is becoming more important in the practice of oncology. The standard for the last several decades is to elect chemotherapeutic agents based on staging and histological identification of the primary cancer site alone versus utilizing the genetic and molecular profile information along with histological primary cancer site and staging to select chemotherapy regimens. Cancers are caused by mutations that occur within cells and therefore selecting treatment based on mutations and not primary cancer site alone can provide advantages that may have gone overlooked. As time progresses, more biomarkers continue to be discovered which can lead to more targets for drugs either currently on the market or clinical trials. In addition to advancements made in the progression of cancer treatment with utilizing molecular profiles effectively, there are other therapeutic strategies that have been postulated as advanced effective ways to administer chemotherapy. These strategies provide chemotherapy to patients while fasting, giving insulin or other biological response modifiers adjunctively prior to chemotherapy for enhanced targeting, and giving chemotherapy in micro-doses to allow for increased frequency of administration and the utilization of multiple targeted chemotherapeutic agents concurrently. In this paper we will discuss these topics and explain their benefits in addition to the evidence that supports these treatments. A review on biomarkers and cancer cell metabolism is discussed as it relates to providing a framework for what constitutes a biomarker in addition to what metabolic processes are related to fasting and administering insulin with chemotherapy. The information provid

关键词： Biomarkers Molecular Profile Cancer Chemotherapy Glycolysis Insulin

Autologous Natural Killer Cell/Natural Killer T Cell Immunotherapy of Malignant Diseases

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Open journal of Medical Microbiology 2014年第3期4卷 192-202页

作者： Aaron j. Smith john Oertle dino Prato Envita Scottsdale AZ USA

Adoptive immunotherapy, the therapeutic infusion of ex vivo activated cancer-fighting white blood cells that was pioneered by Dr. Steven Rosenberg over 30 years ago, has become more widespread due to outstanding published research documenting the clinical efficacy of this strategy. Based on the well-established in vivo functions of NK and NKT cells, their integral role in the efficacy of certain chemotherapeutic and immunomodulatory agents, and their direct therapeutic action as displayed in clinical trials, the use of autologous natural killer cell infusions is an appropriate and warranted therapeutic option for the treatment of malignant diseases, especially in patients whose disease is refractory to standard treatments such as chemotherapy and radiation.

关键词： Cancer Immunotherapy Autologous Natural Killer Cells (NK Cells) Natural Killer T Cell (NKT Cells) Lymphocyte Activated Killer Cells (LAK cells)

Chronic Lyme Disease: Persistent Clinical Symptoms Related to Immune Evasion, Antibiotic Resistance and Various Defense Mechanisms of Borrelia burgdorferi

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Open journal of Medical Microbiology 2014年第4期4卷 252-260页

作者： Aaron j. Smith john Oertle dino Prato Envita Scottsdale AZ USA

There are several factors involved in the ability of Borrelia burgdorferi to retain a persistent infection within a mammalian host. These factors of immune evasion include regulation of membrane proteins, variable epitopes of surface proteins, protection against the immune system through tick saliva, the ability to migrate to regions where it is not exposed to the immune system or antibiotics, invagination or invasion within various cells, pleomorphic forms, and the potential to produce biofilms. The window of conventional treatment for Lyme disease is short and has the potential to display different symptoms depending on the strain of Borrelia bugdorferi. These symptoms are dependent on the localization of Borrelia burgdorferi which correlates to the significance of diagnosing Lyme disease early to prevent such a spread throughout the body. Such complications of Borrelia burgdorferi may demand new clinical treatment discoveries for patient fighting the chronic form.

关键词： Borrelia burgdorferi Immune Response Antibiotics Surface Proteins Pleomorphism Ixode Tick

Multiple Actions of Curcumin Including Anticancer, Anti-Inflammatory, Antimicrobial and Enhancement via Cyclodextrin

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journal of Cancer Therapy 2015年第3期6卷 257-272页

作者： Aaron j. Smith john Oertle dino Prato Envita Scottsdale USA

Curcumin is a naturally occurring phytotherapeutic that has broad uses including the treatment of cancer and as a potent antimicrobial agent. Its dynamic ability to treat very different kinds of disease has spawned a significant increase in inquiry on how curcumin accomplishes these feats. Thousands of peer reviewed papers were published in the past few years regarding the various functions of curcumin. Unlike most pharmaceuticals, curcumin has a multi-range of different targets that it interacts with. Since curcumin’s bioavailabilty is limited, methods of increasing curcumin’s bioavailabilty are discussed. Mechanisms of action regarding curcumin’s ability to effect cancer are discussed including upstream and downstream mechanisms starting with epigenetics to its effect on signal transduction pathways and apoptosis. Curcumin also works adjuvantly with chemotherapy to reduce resistance and enhance the mechanism of certain chemotherapeutic agents. Curcumin’s antibacterial, antifungal, and antiviral capability is also discussed with regard to curcumin’s dynamic ability to treat infections. Curcumin use in cancer adjunctive care and its anti-infectious capabilities make it a unique phytotherapeutic agent with promise.

关键词： Curcumin Cancer Chemotherapy Anti-Inflammatory Antimicrobial Cyclodextrin

Borreliaburgdorferi: Cell Biology and Clinical Manifestations in Latent Chronic Lyme

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Open journal of Medical Microbiology 2014年第4期4卷 210-223页

作者： Aaron j. Smith john Oertle dino Prato Envita Scottsdale AZ USA

Chronic Lyme disease is predicated by an infection with Borrelia burgdorferi via tick vector. B. burgdorferi has been extensively researched with regard to its genome and cell biology. There are many unique characteristics to the bacteria itself;however, serological diagnostics and diagnosis based on symptoms can be complicated and potentially misleading. Other promising diagnostics were also evaluated in this review. Treatment of the chronic Lyme disease can be complicated and at times ineffective. The purpose of this review is to examine B. burgdorferi from a biological and clinical perspective.

关键词： Lyme Disease Borrelia Burgdorferi Genome Cellular Process Epidemiology CD57 C4a Diagnostics Treatment

Cancer and Infectious Causes

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Open journal of Medical Microbiology 2014年第3期4卷 161-177页

作者： Aaron j. Smith john Oertle dino Prato Envita Scottsdale AZ USA

Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention and targeting of cancer therapy. Although nearly 20% of all cancers are caused by an infection of a microbe, the amount of evidence and information regarding the mechanisms associated with oncogenesis varies dramatically from one organism to the next. This review cannot be exhaustive because we are not aware of all infections worldwide in addition to their potential mechanisms for oncogenesis. More research is required for all of the species mentioned in this review.

关键词： Epstein Bar Virus Hepatitis B Virus Hepatitis C Virus Human Herpes Virus 6 Human Herpes Virus 8 Human Papillomavirus Human T-Cell Leukemia Virus Type 1 Merkel Cell Polyomavirus Chlamydia pneumonia Helicobacter pylori Mycoplasma Salmonella typhi-1 Streptococcus bovis Clonorchis sinensis Opisthorchis viverrini Schistosoma haematobium Aspergillus flavus Aspergillus parasiticus Cancer Oncogenesis

Novel Approach to Chemotherapy and Administration Selection with Metronomic/Fractionated Dosing

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journal of Cancer Therapy 2015年第5期6卷 455-465页

作者： Aaron j. Smith john Oertle dino Prato Envita Scottsdale AZ USA

Metronomic dosing of chemotherapy was introduced in the early 2000s and has since gained recognition as a potential game changer in the manner of which chemotherapy can be administered. There are several known candidates for metronomic dosing of chemotherapy with the potential for many more to be elucidated in the future. Minimized overall side effects, longer durations of treatment, potential minimization of multidrug resistance (MDR) mutations, potential less refractory responses, and the potential to safely use more than one chemotherapy treatments also make metronomic dosing of chemotherapy attractive. Metronomic dosing reduces common side effects and has the potential to reduce neutropenia, lymphocytopenia, and cognitive changes associated with maximum tolerated dosages (MTD). Methods of enhancing chemotherapy including fasting and administration of insulin are also discussed. Metronomic dosing combined with a patient’s molecular profile derived from biomarkers is particularly exciting. It holds significant potential with regard to administrating the most relevant chemotherapies and offers maximal beneficial results.

关键词： Metronomic Dosing Chemotherapy Multidrug Resistance Neutropenia Lymphocytopenia Insulin Biomarkers Cognitive Changes