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Аутоиммунные заболевания в эпоху COVID-19:: новые механизмы, клинические последствия, соображения, связанные с вакцинацией, и направления будущей деятельности.

Болезнь коронавируса 2019 (В тыс.COVID-19) пандемия высветила сложную двунаправленную связь между SARSCoV-2 инфекция и аутоиммунные заболевания. В настоящем обзоре рассматривается вопрос о том, каким образом SARS-CoV-2 Инфекция влияет на частотность, прогресс и результаты five Крупные аутоиммунные заболевания: системный волшебный эритематос, ревматоидный артрит, множественный склероз, воспалительный кишечник и синдром Гильен-Барре. Пациенты с аутоиммунными заболеваниями подвергаются повышенному риску серьезных заболеваний. COVID-19 Из-за иммунной дисрегуляции и использования иммуновосприимчиво

К лечению множественных склерозов

Множественный склероз (MS) является воспалительным и демиелинизирующим заболеванием центральной нервной системы (CNS). У большинства пациентов болезнь начинается с острого наступления, за которым следует этап ремиссии, последующие рецидивы и позднее переход к устойчивой хронической прогрессии. В меньшинстве пациентов эта постепенная фаза развивается с самого начала. Для рецидивов MS характерно в основном деновое образование побочного повреждения CNS и инфильтрация иммунных клеток, в то время как патологические особенности MS прогрессирования включают медленно расширяющиеся повреждения, глобаль

Keyword Index for Volume 95

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Glucosylsphingosine (Lyso-Gb1) as a reliable biomarker in Gaucher disease: a narrative review.

BACKGROUND: Gaucher disease (GD) is a rare, inherited, autosomal recessive disorder caused by a deficiency of the lysosomal enzyme, acid β-glucosidase. Its diagnosis is achieved via measurements of acid β-glucosidase activity in either fresh peripheral blood leukocytes or dried blood spots, and confirmed by identifying characteristic mutations in the GBA1 gene. Currently, several biomarkers are available for disease monitoring. Chitotriosidase has been used over the last 20 years to assess the severity of GD, but lacks specificity in GD patients. Conversely, the deacylated form of glucosylcera

B-cells in pulmonary arterial hypertension: friend, foe or bystander?

There is an unmet need for new therapeutic strategies that target alternative pathways to improve the prognosis of patients with pulmonary arterial hypertension (PAH). As immunity has been involved in the development and progression of vascular lesions in PAH, we review the potential contribution of B-cells in its pathogenesis and evaluate the relevance of B-cell-targeted therapies. Circulating B-cell homeostasis is altered in PAH patients, with total B-cell lymphopenia, abnormal subset distribution (expansion of naïve and antibody-secreting cells, reduction of memory B-cells) and chronic acti

Рак у пациентов, страдающих множественным склерозом, после длительного воздействия на них методов лечения, направленных на изменение болезней (ДМТ): систематический обзор и метаанализ.

ВВЕДЕНИЕ: Нынешняя литература, посвященная распространенности и потенциальной связи между лечением, позволяющим регулировать заболевания (ДМТ), и риском раковых заболеваний среди населения, занимающегося НР, дает неоднозначные результаты. МЕТОДЫ: Данное исследование было направлено на оценку распространенности рака и риска заболевания раком у пациентов с синдромом MS (PwMS) при длительном воздействии DMT. Поиск базы данных включает: MedLINE PUBMED, SCOPUS и Google Scientific. РЕЗУЛЬТАТЫ: Всего 13 исследования, связанные 333,779 В нее были включены PwMS, сообщающие о раковых заболеваниях за раз

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… Sphingosine 1-Phosphate Receptor (S1PR) modulators such as Siponimod and fingolimod have been shown to inhibit sphingosine kinase 1 (SK1). This enzyme is upregulated in various forms cancers, including CNS, gastrointestinal tract, genitourinary system, lungs, and breast cancers [ 33 , 34 ]. …

Действенность и безопасность оральных препаратов, изменяющих болезни, при лечении повторно излучающего многообразного склероза: систематический обзор и сетевой метаанализ.

КОЛИЧЕСТВО: Повторный множественный склероз (RRMS) является хроническим воспалительным демиелинистическим заболеванием, затрагивающим центральную нервную систему и характеризующимся сложным патогенезом и увеличением годовой заболеваемости. Несмотря на то, что в настоящее время клинические мероприятия в рамках ОРУО носят разнообразный характер, по-прежнему относительно мало прямых сравнительных исследований по вопросам эффективности и безопасности различных перорально-модифицирующих препаратов, что приводит к недостаточности всеобъемлющих данных.ЦЕЛЬ: Цель настоящего исследования заключается в

Don't eat me/eat me signals as a novel strategy in cancer immunotherapy.

Cancer stands as one of the prominent global causes of death, with its incidence burden continuously increasing, leading to a substantial rise in mortality rates. Cancer treatment has seen the development of various strategies, each carrying its drawbacks that can negatively impact the quality of life for cancer patients. The challenge remains significant within the medical field to establish a definitive cancer treatment that minimizes complications and limitations. In the forthcoming years, exploring new strategies to surmount the failures in cancer treatment appears to be an unavoidable pur

Curcumol inhibits the malignant progression of prostate cancer and regulates the PDK1/AKT/mTOR pathway by targeting miR‑9.

Curcumol has been reported to exert anti‑tumor activity, but its intrinsic molecular mechanism in prostate cancer remains to be elucidated. The present study aimed to analyze the effect of curcumol on prostate cancer and identify its possible internal regulatory pathway using in vitro cell culture and in vivo tumor model experiments. The cytotoxicity of curcumol was detected using a Cell Counting Kit‑8 assay and it was found that curcumol had no obvious toxicity or side effects on RWPE‑1 cells. Wound healing, Transwell and flow cytometry assays demonstrated that curcumol could affect the activ

Advances in antisense oligonucleotide development for target identification, validation, and as novel therapeutics.

Antisense oligonucleotides (As-ODNs) are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18-21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind cognate mRNA sequences by sequence-specific hybridization. This results in cleavage or disablement of the mRNA and, thus, inhibits the expression of the target gene. The specificity of the As approach is based on the probability that, in the human genome, any sequence longer than a minimal number of nucleotides (nt), 13 for RNA and 17 for DNA, normal

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… One example of the use of As-ODNs in target identification/validation is the identification of Sphingosine Kinase-1 (SPHK-1) as a key player in the pro-inflammatory responses triggered by TNFα in human monocytes [ 153 ] and by C5a in human monocyte-derived macrophages [ 154 ]. … Sphingosine kinase 1 regulates pro-inflammatory responses triggered by TNFalpha in primary human monocytes. J. Cell. Physiol. 2006;208(1):109–15. doi: 10.1002/jcp.20646. 154. Melendez AJ, Ibrahim FB. …

Coming of Age for Autotaxin and Lysophosphatidate Signaling: Clinical Applications for Preventing, Detecting and Targeting Tumor-Promoting Inflammation.

A quarter-century after the discovery of autotaxin in cell culture, the autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis is now a promising clinical target for treating chronic inflammatory conditions, mitigating fibrosis progression, and improving the efficacy of existing cancer chemotherapies and radiotherapy. Nearly half of the literature on this axis has been published during the last five years. In cancer biology, LPA signaling is increasingly being recognized as a central mediator of the progression of chronic inflammation in the establishment of a tumor microenvironmen

Morpholino-driven blockade of Dkk-1 in osteosarcoma inhibits bone damage and tumour expansion by multiple mechanisms.

BackgroundOsteosarcoma (OS) is the most common primary bone malignancy. Chemotherapy plays an essential role in OS treatment, potentially doubling 5-year event-free survival if tumour necrosis can be stimulated. The canonical Wnt inhibitor Dickkopf-1 (Dkk-1) enhances OS survival in part through upregulation of aldehyde-dehydrogenase-1A1 which neutralises reactive oxygen species originating from nutritional stress and chemotherapeutic challenge.MethodsA vivo morpholino (DkkMo) was employed to block the expression of Dkk-1 in OS cells. Cell mitosis, gene expression and bone destruction were meas

The Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases.

PurposeIn 2007 the two senior authors wrote a review on the structure and function of the endothelial glycocalyx layer (Weinbaum in Annu Rev Biomed Eng 9:121-167, 2007). Since then there has been an explosion of interest in this hydrated gel-like structure that coats the luminal surface of endothelial cells that line our vasculature due to its important functions in (A) basic vascular physiology and (B) vascular related diseases. This review will highlight the major advances that have occurred since our 2007 paper.MethodsA literature search mainly focusing on the role of the glycocalyx in the

Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications.

The insufficient and unspecific target of traditional therapeutic approaches in cancer treatment often leads to therapy resistance and cancer recurrence. Over the past decades, accumulating discoveries about stem cell biology have provided new potential approaches to cure cancer patients. Stem cells possess unique biological actions, including self-renewal, directional migration, differentiation, and modulatory effects on other cells, which can be utilized as regenerative medicine, therapeutic carriers, drug targeting, and generation of immune cells. In this review, we emphasize the mechanisms

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma.

Autophagy is a multistep catabolic process through which misfolded, aggregated or mutated proteins and damaged organelles are internalized in membrane vesicles called autophagosomes and ultimately fused to lysosomes for degradation of sequestered components. The multistep nature of the process offers multiple regulation points prone to be deregulated and cause different human diseases but also offers multiple targetable points for designing therapeutic strategies. Cancer cells have evolved to use autophagy as an adaptive mechanism to survive under extremely stressful conditions within the tumo

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… The study using HCQ combines this autophagy inhibitor with ABC294640 (Opaganib), a first-in-class sphingosine kinase-2 (SK2)-selective inhibitor. …

Protein Quality Control in Glioblastoma: A Review of the Current Literature with New Perspectives on Therapeutic Targets.

Protein quality control allows eukaryotes to maintain proteostasis under the stress of constantly changing conditions. In this review, we discuss the current literature on PQC, highlighting flaws that must exist for malignancy to occur. At the nidus of PQC, the expression of BAG1-6 reflects the cell environment; each isoform directs proteins toward different, parallel branches of the quality control cascade. The sum of these branches creates a net shift toward either homeostasis or apoptosis. With an established role in ALP, Bag3 is necessary for cell survival in stress conditions including th

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… The compensatory response of ALP in the absence of the UPS has been circumvented with the knock-out of the Bag3 gene or the inhibition of the autophagy stimulator sphingosine kinase 2 [ 126 , 127 ], suggesting that repression of autophagy is ultimately necessary to ensure consistent cell death. 3.4. … Resensitising proteasome inhibitor-resistant myeloma with sphingosine kinase 2 inhibition Neoplasia 2022 24 1 11 10.1016/j.neo.2021.11.009 34826777 PMC8626806 127. Fernández Á.F. Sebti S. Wei Y. Zou Z. Shi M. McMillan K.L. He C. Ting T. Liu Y. Chiang W.C. …

The Role of Extracellular Vesicles in Bone Metastasis.

Multiple types of cancer have the specific ability to home to the bone microenvironment and cause metastatic lesions. Despite being the focus of intense investigation, the molecular and cellular mechanisms that regulate the metastasis of disseminated tumor cells still remain largely unknown. Bone metastases severely impact quality of life since they are associated with pain, fractures, and bone marrow aplasia. In this review, we will summarize the recent discoveries on the role of extracellular vesicles (EV) in the regulation of bone remodeling activity and bone metastasis occurrence. Indeed,

Progressive multiple sclerosis: Evaluating current therapies and exploring future treatment strategies.

Progressive forms of multiple sclerosis (MS) include primary progressive MS (PPMS) and secondary progressive MS (SPMS). Unlike relapsing-remitting MS (RRMS), progressive MS is recognized by relentless progression with accumulating disability, rare to no relapses nor new activity on MRIs. Clinically, neurologic worsening in MS can occur in the relapsing-remitting (RRMS) phase of disease due to incomplete recovery from neuroinflammatory relapses. However, a progressive disease course is the dominant factor related to accumulating disability. There is persistent central nervous system (CNS) compa

Polydatin: Pharmacological Mechanisms, Therapeutic Targets, Biological Activities, and Health Benefits.

Polydatin is a natural potent stilbenoid polyphenol and a resveratrol derivative with improved bioavailability. Polydatin possesses potential biological activities predominantly through the modulation of pivotal signaling pathways involved in inflammation, oxidative stress, and apoptosis. Various imperative biological activities have been suggested for polydatin towards promising therapeutic effects, including anticancer, cardioprotective, anti-diabetic, gastroprotective, hepatoprotective, neuroprotective, anti-microbial, as well as health-promoting roles on the renal system, the respiratory s

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… In addition, polydatin attenuated the activity of hepatic stellate cells (HSCs) through its antioxidant activity on sphingosine kinase 1 (SphK1) signaling to ameliorate mice liver fibrosis induced by carbon tetrachloride (CCl4) [ 73 ]. … Polydatin attenuates hepatic stellate cell proliferation and liver fibrosis by suppressing sphingosine kinase 1 Biomed. Pharmacother. 2020 130 110586 10.1016/j.biopha.2020.110586 34321171 74. Carson D.A. Ribeiro J.M. …

Advances in the treatment of systemic lupus erythematosus: Biologicals, small-molecular agents, and cell-depleting therapies coming to the clinic.

Systemic lupus erythematosus (SLE; lupus) remains a particular challenge for the practicing clinician on account of its chronic undulating and unpredictable course, its diverse manifestations, and-until recently-limited treatment options all associated with considerable downsides. However, a major change in this situation is currently taking place. Over the past few years, several new biological therapeutics have been approved for the treatment of SLE (belimumab and anifrolumab) or specifically for its renal organ manifestation (obinutuzumab), along with one new small molecular treatment for t