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Role of T cells and cytokines in the pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a long-term autoimmune disease. It causes persistent joint inflammation, aberrant tissue growth, and progressive joint deterioration. T cells have a key role in the onset of RA. They identify and trigger other immune cells, and produce inflammatory signals such as interleukin-6 (IL-6), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α). Prolonged inflammation and tissue damage are caused by an imbalance between regulatory T cells (Tregs) and pro-inflammatory T helper 17 (Th17) cells. Additionally, the condition is exacerbated by uncontrolled cytokine netwo

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… Biomarkers of T cell T cells are essential in the therapy of RA, facilitating neoangiogenesis, lymphoid organogenesis, and osteoclastogenesis. …

Uncommon Factors Leading to Nephrotic Syndrome.

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransfe

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… The researchers believe that the pleiotropic effects during organogenesis attest to the broad regulatory function of LMX1B. …

Методологии изучения мозговых органоидов для изучения механизмов заболевания в прогрессивном множественном склерозе.

Множественный склероз (MS) — изнуряющее аутоиммунное расстройство, направленное против центральной нервной системы (CNS), отмечен непрерывным обезвоживанием и воспалением. В клинической форме она представляет в трех различных формах: повторные выбросы MS (RRMS), первичные прогрессивные MS (PPMS) и вторичные прогрессивные MS (SPMS). Несмотря на то, что лечение с целью изменения болезней (ДМР) оказывает определенное содействие людям, страдающим СВЗ, варианты лечения прогрессивных СЗМ (ПМС) по-прежнему являются крайне неадекватными. Этот пробел свидетельствует о настоятельной необходимости примен

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… Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345:125. doi: 10.1126/science.1247125 Lancaster M. A., Renner M., Martin C. A., Wenzel D., Bicknell L. S., Hurles M. E., et al. (2013). Cerebral organoids model human brain development and microcephaly. …

Oncolytic virus-based hepatocellular carcinoma treatment: Current status, intravenous delivery strategies, and emerging combination therapeutic solutions.

Current treatments for advanced hepatocellular carcinoma (HCC) have limited success in improving patients' quality of life and prolonging life expectancy. The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies. Recently, there has been increased interest in oncolytic viruses (OVs) as a therapeutic modality for HCC. OVs undergo selective replication in cancerous tissues and kill tumor cells. Strikingly, pexastimogene devacirepvec (Pexa-Vec) was granted an orphan drug status in HCC by the U.S. Food and Drug Administration (FDA) in 2013.

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… Wnt signal transduction pathways Organogenesis 4 2 2008 68 75 19279717 10.4161/org.4.2.5851 PMC2634250 29 Kim S. Jeong S. Mutation hotspots in the β-catenin gene: lessons from the human cancer genome databases Mol Cells 42 1 2019 8 16 30699286 10.14348/molcells.2018.0436 PMC6354055 30 Wang R. …

Osteonecrosis of the Jaw and Antiresorptive Agents in Benign and Malignant Diseases: A Critical Review Organized by the ECTS.

CONTEXT: Antiresorptive therapy significantly reduces fracture risk in patients with benign bone disease and skeletal-related events (SREs) in patients with bone metastases (BM). Osteonecrosis of the jaw (ONJ) is a rare but severe condition manifested as necrotic bone lesion or lesions of the jaws. ONJ has been linked to the use of potent antiresorptive agents, termed medication-related ONJ (MRONJ). OBJECTIVE: We aimed to identify the differences various aspects of MRONJ among distinct patient categories and provide recommendations on how to mitigate the risk and optimally manage MRONJ in eac

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… OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis . Nature. 1999 ; 397 ( 6717 ): 315 - 323 . 9950424 10.1038/16852 2. Bilezikian JP . Efficacy of bisphosphonates in reducing fracture risk in postmenopausal osteoporosis . …

Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice.

Over the past few decades, there has been growing interest in understanding the molecular mechanisms of cancer pathogenesis and progression, as it is still associated with high morbidity and mortality. Current management of large bone sarcomas typically includes the complex therapeutic approach of limb salvage or sacrifice combined with pre- and postoperative multidrug chemotherapy and/or radiotherapy, and is still associated with high recurrence rates. The development of cellular strategies against specific characteristics of tumour cells appears to be promising, as they can target cancer cel

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… EMT-mediated supplementation of a tumour Epithelial to mesenchymal transition (EMT) has a crucial role in organogenesis, wound healing, tumour progression and metastasis. …

Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.

The past decade has seen significant advances in our understanding of Hedgehog (HH) signaling pathway in various biological events. HH signaling pathway exerts its biological effects through a complex signaling cascade involved with primary cilium. HH signaling pathway has important functions in embryonic development and tissue homeostasis. It plays a central role in the regulation of the proliferation and differentiation of adult stem cells. Importantly, it has become increasingly clear that HH signaling pathway is associated with increased cancer prevalence, malignant progression, poor progn

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… important roles in transforming normal prostate basal/stem cells into PCa stem cells. 262 In addition, inhibition of Shh signaling pathway showed potential for prevention of drug resistance such as zoledronic acid. 263 Liver tumor HH signaling pathway is considered to play an essential role in liver organogenesis …

Male Lower Urinary Tract Dysfunction: An Underrepresented Endpoint in Toxicology Research.

Lower urinary tract dysfunction (LUTD) is nearly ubiquitous in men of advancing age and exerts substantial physical, mental, social, and financial costs to society. While a large body of research is focused on the molecular, genetic, and epigenetic underpinnings of the disease, little research has been dedicated to the influence of environmental chemicals on disease initiation, progression, or severity. Despite a few recent studies indicating a potential developmental origin of male LUTD linked to chemical exposures in the womb, it remains a grossly understudied endpoint in toxicology research

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… Similarly, mouse prostate organogenesis is like that of the human prostate [ 109 ]. These data support the use of mice as a relevant model species for studying cellular and molecular mechanisms of benign prostatic disease. …

The Bone Marrow Microenvironment Mechanisms in Acute Myeloid Leukemia.

Bone marrow (BM) is a highly complex tissue that provides important regulatory signals to orchestrate hematopoiesis. Resident and transient cells occupy and interact with some well characterized niches to produce molecular and cellular mechanisms that interfere with differentiation, migration, survival, and proliferation in this microenvironment. The acute myeloid leukemia (AML), the most common and severe hematological neoplasm in adults, arises and develop in the BM. The osteoblastic, vascular, and reticular niches provide surface co-receptors, soluble factors, cytokines, and chemokines that

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… Whether in the organogenesis of bone marrow or in the homeostatic response to several stimuli, angiogenesis is a physiological process co-regulated by osteoblasts and performs an important function in the vascular niche ( Schipani et al., 2013 ). …

Advances in microsurgery and assisted reproduction for management of male infertility.

BACKGROUND: This study examines genetic diversity among 102 registered English Bulldogs used for breeding based on maternal and paternal haplotypes, allele frequencies in 33 highly polymorphic short tandem repeat (STR) loci on 25 chromosomes, STR-linked dog leukocyte antigen (DLA) class I and II haplotypes, and the number and size of genome-wide runs of homozygosity (ROH) determined from high density SNP arrays. The objective was to assess whether the breed retains enough genetic diversity to correct the genotypic and phenotypic abnormalities associated with poor health, to allow for the elimi

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… Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays. Cell. 2022;185(10):1777-1792 e21. 45. Chen KH, et al. RNA imaging. Spatially resolved, highly multiplexed RNA profiling in single cells. Science. 2015;348(6233):aaa6090. 46. Shah S, et al. …

Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.

Tumors are highly dynamic diseases characterized by significant heterogeneity. They consist of multiple cellular populations with distinct properties that respond differently to therapeutic pressure. This heterogeneity may arise from spatial variation across tumor regions (spatial heterogeneity) as well as from temporal changes during tumor evolution and treatment (temporal heterogeneity). As a consequence, drug-resistant subclones often emerge under therapy and contribute to treatment failure. Advances in single-cell and spatial multi-omics technologies enable precise quantification of tumor

Lost in Translation (LiT): IUPHAR Review 6.

Translational medicine is a roller coaster with occasional brilliant successes and a large majority of failures. Lost in Translation 1 ('LiT1'), beginning in the 1950s, was a golden era built upon earlier advances in experimental physiology, biochemistry and pharmacology, with a dash of serendipity, that led to the discovery of many new drugs for serious illnesses. LiT2 saw the large-scale industrialization of drug discovery using high-throughput screens and assays based on affinity for the target molecule. The links between drug development and university sciences and medicine weakened, but t

Tumor biomarkers for diagnosis, prognosis and targeted therapy.

Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecu

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… ccRCC) patients with high levels of VEGF. 401 In summary, circulating VEGF and VEGFR-2 have been used as crucial biomarkers for the prediction of prognosis and antiangiogenic drug efficacy. 405 , 421 FGF Fibroblast growth factor (FGF) is a secreted glycoprotein 422 that engages in the regulation of organogenesis …

The regulatory networks and mechanisms of bone microenvironment in tumorigenesis and metastasis.

Bone tumors, encompassing heterogeneous primary and metastatic lesions, are driven in their initiation, progression, and metastasis by dysregulation of the bone microenvironment (BME). Clinically manifested by localized pain, pathological fractures, and neurological deficits, these malignancies substantially threaten patient survival. Radiographic patterns (osteolytic, osteoblastic, mixed) directly reflect pathogenic BME-tumor interactions, particularly involving osteoblast-osteoclast imbalance. The BME-a specialized niche of bone-resident cells (osteocytes, osteoblasts, osteoclasts), immune c

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… Wingless/integrated β-catenin signaling pathway The Wnt/β-catenin signaling pathway is a highly conserved pathway critically involved in essential biological processes, including cell growth and development, organogenesis, tissue homeostasis, and disease progression. [ 53 ] This pathway operates through …

The Impact of Human Microbiotas in Hematopoietic Stem Cell and Organ Transplantation.

The human microbiota heavily influences most vital aspects of human physiology including organ transplantation outcomes and transplant rejection risk. A variety of organ transplantation scenarios such as lung and heart transplantation as well as hematopoietic stem cell transplantation is heavily influenced by the human microbiotas. The human microbiota refers to a rich, diverse, and complex ecosystem of bacteria, fungi, archaea, helminths, protozoans, parasites, and viruses. Research accumulating over the past decade has established the existence of complex cross-species, cross-kingdom interac

An Updated Review on Marine Anticancer Compounds: The Use of Virtual Screening for the Discovery of Small-Molecule Cancer Drugs.

Marine secondary metabolites are a promising source of unexploited drugs that have a wide structural diversity and have shown a variety of biological activities. These compounds are produced in response to the harsh and competitive conditions that occur in the marine environment. Invertebrates are considered to be among the groups with the richest biodiversity. To date, a significant number of marine natural products (MNPs) have been established as antineoplastic drugs. This review gives an overview of MNPs, both in research or clinical stages, from diverse organisms that were reported as bein

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… This process occurs during organogenesis or in a damaged organ and is involved in wound-healing activity, menstruation and placenta formation during pregnancy. …

miR-708-5p: a microRNA with emerging roles in cancer.

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression post-transcriptionally. They are crucial for normal development and maintaining homeostasis. Researchers have discovered that dysregulated miRNA expression contributes to many pathological conditions, including cancer. miRNAs can augment or suppress tumorigenesis based on their expression and transcribed targetome in various cell types. In recent years, researchers have begun to identify miRNAs commonly dysregulated in cancer. One recently identified miRNA, miR-708-5p, has been shown to have profound roles in

Extraskeletal benefits and risks of calcium, vitamin D and anti-osteoporosis medications.

UnlabelledDrugs used for the prevention and the treatment of osteoporosis exert various favourable and unfavourable extra-skeletal effects whose importance is increasingly recognized notably for treatment selection.IntroductionThe therapeutic armamentarium for the prevention and the treatment of osteoporosis is increasingly large, and possible extra-skeletal effects of available drugs could influence the choice of a particular compound.MethodsThe present document is the result of a national consensus, based on a systematic and critical review of the literature.ResultsObservational research has

Commercially available bioinks and state-of-the-art lab-made formulations for bone tissue engineering: A comprehensive review.

Bioprinting and bioinks are two of the game changers in bone tissue engineering. This review presents different bioprinting technologies including extrusion-based, inkjet-based, laser-assisted, light-based, and hybrid technologies with their own strengths and weaknesses. This review will aid researchers in the selection and assessment of the bioink; the discussion ranges from commercially available bioinks to custom lab-made formulations mainly based on natural polymers, such as agarose, alginate, gelatin, collagen, and chitosan, designed for bone tissue engineering. The review is centered on

Exploring the dual role of B cells in solid tumors: implications for head and neck squamous cell carcinoma.

In the tumor milieu of head and neck squamous cell carcinoma (HNSCC), distinct B cell subpopulations are present, which exert either pro- or anti-tumor activities. Multiple factors, including hypoxia, cytokines, interactions with tumor cells, and other immune infiltrating lymphocytes (TILs), alter the equilibrium between the dual roles of B cells leading to cancerogenesis. Certain B cell subsets in the tumor microenvironment (TME) exhibit immunosuppressive function. These cells are known as regulatory B (Breg) cells. Breg cells suppress immune responses by secreting a series of immunosuppressi