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Adjuvant doxycycline to enhance anti-amyloid effects: Results from the dual phase 2 trial.

BackgroundAlthough, doxycycline use is associated with improved outcomes in amyloidosis in retrospective studies, evidence from clinical trials is limited.MethodsThis phase 2 trial of doxycycline (clinicaltrials.gov: NCT02207556) in newly diagnosed light chain (AL) amyloidosis enrolled 25 patients with systemic AL amyloidosis on treatment with doxycycline for 1 year along with chemotherapy. Outcomes of interest included mortality, organ response, and hematologic response rates at 1 year.FindingsThe median age was 62 years, 64% were male, and 68% had the AL lambda subtype. Patients had Mayo 201

Modulation of Angiogenic Processes by the Human Gammaherpesviruses, Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus.

Angiogenesis is the biological process by which new blood vessels are formed from pre-existing vessels. It is considered one of the classic hallmarks of cancer, as pathological angiogenesis provides oxygen and essential nutrients to growing tumors. Two of the seven known human oncoviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), belong to the Gammaherpesvirinae subfamily. Both viruses are associated with several malignancies including lymphomas, nasopharyngeal carcinomas, and Kaposi's sarcoma. The viral genomes code for a plethora of viral factors, includin

Increased risk of bisphosphonate-related osteonecrosis of the jaw in patients with Sjögren's syndrome: nationwide population-based cohort study.

OBJECTIVE: The aim of this study was to explore whether patients with Sjögren's syndrome (SS) were susceptible to bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) after tooth extraction in the entire population of Taiwan. DESIGN: A nationwide population-based retrospective cohort study. SETTING: Data were extracted from Taiwan's National Health Insurance Research Database (NHIRD). METHODOLOGY: Medical conditions for both the study and control group were categorised using the International Classification of Diseases, 9th Revision. ORs and 95% CIs for associations between SS and o

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… Basi DL , Hughes PJ , Thumbigere-Math V , et al Matrix metalloproteinase-9 expression in alveolar extraction sockets of Zoledronic acid-treated rats . J Oral Maxillofac Surg 2011 ; 69 : 2698 – 707 . 10.1016/j.joms.2011.02.065 21752506 28. … Hulkkonen J , Pertovaara M , Antonen J , et al Matrix metalloproteinase 9 (MMP-9) gene polymorphism and MMP-9 plasma levels in primary Sjogren’s syndrome . Rheumatology 2004 ; 43 : 1476 – 9 . 10.1093/rheumatology/keh369 15316122 33. …

Ferret coronavirus-associated diseases.

A novel coronavirus of ferrets was first described in 1993. This coronavirus caused an enteric disease called epizootic catarrhal enteritis (ECE). Recently, a ferret systemic coronavirus (FRSCV)-associated disease was discovered. This new systemic disease resembles the dry form of feline infectious peritonitis (FIP) and has been reported in the United States and Europe. This article addresses the clinical signs, pathology, pathogenesis, diagnosis, treatment, and prevention of this ferret FIP-like disease.

The genetic architecture of bone metastases: unveiling the role of epigenetic and genetic modifications in drug resistance.

Bone metastases represent frequent and severe complications in various cancers, notably impacting prognosis and quality of life. This review article delves into the genetic and epigenetic mechanisms underpinning drug resistance in bone metastases, a key challenge in effective cancer treatment. The development of drug resistance in cancer can manifest as either intrinsic or acquired, with genetic heterogeneity playing a pivotal role. Intrinsic resistance is often due to pre-existing mutations, while acquired resistance evolves through genetic and epigenetic alterations during treatment. These a

Identification of Key Genes and Pathways in Myeloma side population cells by Bioinformatics Analysis.

Background: Multiple myeloma (MM) is the second most common hematological malignancy, which is still incurable and relapses inevitably, highlighting further understanding of the possible mechanisms. Side population (SP) cells are a group of enriched progenitor cells showing stem-like phenotypes with a distinct low-staining pattern with Hoechst 33342. Compared to main population (MP) cells, the underlying molecular characteristics of SP cells remain largely unclear. This bioinformatics analysis aimed to identify key genes and pathways in myeloma SP cells to provide novel biomarkers, predict MM

Disruption of the microenvironmental ecosystem in subchondral bone marrow lesions: Roles in osteoarthritis pathophysiology, pain and progression.

This narrative review explores the role of subchondral bone in the pathophysiology of osteoarthritis (OA), emphasizing the biomechanical and biochemical contributions that it makes to disease progression. A fresh perspective is presented by the authors in the form of a novel hypothesis that implicates mechano-inflammatory disruption of the bone marrow (BM) microenvironmental ecosystem (BM niche), unresolved inflammation, and fibrosis as key drivers of OA pathogenesis and pain. BMLs, detectable via magnetic resonance imaging (MRI), serve as dynamic imaging biomarkers that correlate with pain se

Медицинский каннабис и признаки рака: критический обзор.

Онкология остаётся сложным и гетерогенным заболеванием, вызывающим значительную morbidity и mortality по всему миру, несмотря на продвижение в диагностике и лечении. Характерные черты онкологии раскрывают биологические механизмы, поддерживающие развитие опухолей и злокачественное эволюцию, а также помогают выявить потенциальные мишени для терапии. Медикаментозный кресс-масло в основном используется в онкологии для поддерживающей терапии, но растущее предклиническое доказательство указывает на взаимодействие с сигнальными путями, связанными с онкологией. Этот обзорный материал обобщает текущие

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… Lysophosphatidylinositol MAPK | Mitogen-activated protein kinase MDSC | Myeloid-derived suppressor cell MEK | Mitogen-activated protein kinase/extracellular signal-regulated kinase MGMT | O6-methylguanine-DNA methyltransferase MMP | Matrix metalloproteinase MMP-2 | Matrix metalloproteinase 2 protein MMP-9 | Matrix … metalloproteinase 9 protein MMP2 | Matrix metalloproteinase 2 gene MMP9 | Matrix metalloproteinase 9 gene MMPs | Matrix metalloproteinases mTOR | Mechanistic target of rapamycin MYC | MYC proto-oncogene NADPH | Nicotinamide adenine dinucleotide phosphate NF-κB | Nuclear factor kappa-light-chain-enhancer …

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant atten

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… The proteolytic cleavage process is mediated by various intra- and extracellular serine (Ser) and threonine (Thr) proteinases, including matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase 12 (MMP-12), matrix metalloproteinase 14 (MMP-14), a disintegrin and metalloproteinase with thrombospondin …

Proteoglycans as Molecular Regulators of Bone Metastasis: Extracellular Matrix Remodeling, Tumor-Bone Crosstalk, Dormancy, and Therapeutic Opportunities.

Background: Bone metastasis is a frequent and debilitating complication of advanced cancer, particularly in breast and prostate cancer, and is driven by complex interactions among tumor cells, bone-resident cells, immune populations, vascular components, and the extracellular matrix. Within this specialized microenvironment, proteoglycans have emerged as key molecular regulators of tumor-bone crosstalk, matrix remodeling, metastatic niche formation, dormancy, and therapeutic resistance. Methods: We conducted a narrative review using targeted searches of PubMed and Google Scholar for studies pu

Human Amniotic Membrane Dressing as a Non-Surgical Alternative for Extensive Chronic Ulcers: A Comparative Case Study.

Chronic wound management remains a significant clinical challenge, requiring adaptive therapeutic approaches to achieve wound closure that nonetheless frequently prove fruitless. Balancing the initial pro-inflammatory response with debris removal and tissue rebuilding remains elusive in most cases, leading to pain, drastic quality-of-life deterioration, and, eventually, amputation. Meanwhile, patient adherence is an overarching theme. Furthermore, non-surgical alternatives that effectively promote tissue rebuilding are essential for patients seeking to avoid further invasive procedures. We rep

Преодоление сопротивления CD44-overexpressing миэлома через комбинированную терапию с клетками ATRA, борцезомиба и NK.

CD44 — гликпротеин, часто переоцениваемый раком и связанный с плохим прогнозом. Мы проанализировали прогнозируемую значимость CD44 в перевыражении в миеломе (MM) и изучили терапевтическую эффективность сочетания естественной клеточной терапии убийцы (NK) с транс-ретиновой кислотой (ATRA) и борцезомибом (Bor) против CD44-overexpressing Мм. Для оценки результатов выживаемости по отношению к выражению CD44 были проанализированы клинические данные из базы данных CoMMpass. Ячейки NK были расширены за счет здоровых доноров с использованием K562-OX40L-mbIL-18/21 кормовые клетки, дополненные интерлейк

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… metalloproteinase 9 Nuclear factor kappa B Natural killer Overall survival Peripheral blood Propidium iodide Untreated Author contributions SHJ and JJL contributed to conceptualization, supervision, funding acquisition, review, revision, and final approval of the manuscript. … Miletti-González K, Murphy K, Kumaran MN (2012) Identification of function for CD44 intracytoplasmic domain (CD44-ICD): Modulation of matrix metalloproteinase 9 (MMP-9) transcription via novel promoter response element. J Biol Chem 287(23):18995–19007 17. …

Methamphetamine induces transcriptional changes in cultured HIV-infected mature monocytes that may contribute to HIV neuropathogenesis.

HIV-associated neurocognitive impairment (HIV-NCI) persists in 15-40% of people with HIV (PWH) despite effective antiretroviral therapy. HIV-NCI significantly impacts quality of life, and there is currently no effective treatment for it. The development of HIV-NCI is complex and is mediated, in part, by the entry of HIV-infected mature monocytes into the central nervous system (CNS). Once in the CNS, these cells release inflammatory mediators that lead to neuroinflammation, and subsequent neuronal damage. Infected monocytes may infect other CNS cells as well as differentiate into macrophages,

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… One specific DEG that was increased by meth in this pathway is Matrix metalloproteinase-9 (MMP-9) ( Table S1 ). We validated protein expression of MMP-9 because metalloproteinases have been shown to be important in neuropathogenesis ( 48 ). … Relationship between methamphetamine exposure and matrix metalloproteinase 9 expression. Neuroreport. (2008) 19(14):1407–9. doi: 10.1097/WNR.0b013e32830dd606 55. Xue Y, He JT, Zhang KK, Chen LJ, Wang Q, Xie XL. …

Osteoporosis and the Potential of Cell-Based Therapeutic Strategies.

Osteoporosis, the most common chronic metabolic bone disease, is characterized by low bone mass and increased bone fragility. Nowadays more than 200 million individuals are suffering from osteoporosis and still the number of affected people is dramatically increasing due to an aging population and longer life, representing a major public health problem. Current osteoporosis treatments are mainly designed to decrease bone resorption, presenting serious adverse effects that limit their safety for long-term use. Numerous studies with mesenchymal stem cells (MSCs) have helped to increase the knowl

A Triazaspirane Derivative Inhibits Migration and Invasion in PC3 Prostate Cancer Cells.

Cancer is a serious health problem due to the complexity of establishing an effective treatment. The purpose of this work was to evaluate the activity of a triazaspirane as a migration and invasion inhibitor in PC3 prostatic tumor cells through a possible negative regulation of the FAK/Src signal transduction pathway and decreased secretion of metalloproteinases 2 and 9. Molecular docking analysis was performed using Moe 2008.10 software. Migration (wound-healing assay) and invasion (Boyden chamber assay) assays were performed. In addition, the Western blot technique was used to quantify prote

Melphalan flufenamide inhibits osteoclastogenesis by suppressing proliferation of monocytes.

Myeloma bone disease is a major complication in multiple myeloma affecting quality of life and survival. It is characterized by increased activity of osteoclasts, bone resorbing cells. Myeloma microenvironment promotes excessive osteoclastogenesis, a process of production of osteoclasts from their precursors, monocytes. The effects of two anti-myeloma drugs, melphalan flufenamide (melflufen) and melphalan, on the activity and proliferation of osteoclasts and their progenitors, monocytes, were assessed in this study. In line with previous research, differentiation of monocytes was associated wi

Chemokines and their receptors in oral squamous cell carcinoma: mechanisms, clinical significance, and therapeutic implications.

Chemokines, a category of cytokines exhibiting chemotactic properties, have been thoroughly investigated as targets in cancer treatment in recent decades. In oral squamous cell carcinoma (OSCC), a prevalent and high-risk malignancy of the head and neck, chemokines interact with their specific receptors to initiate downstream signaling pathways. This signaling influences not only tumor cell proliferation, migration, invasion, and metastasis of oral cancer cells but also angiogenesis and vascular maturation. Furthermore, they modulate the tumor microenvironment (TME), which consists of diverse c

Soluble Biomarkers of Osteoporosis and Osteoarthritis, from Pathway Mapping to Clinical Trials: An Update.

Serum biomarkers of osteoarticular diseases have been in the limelight of current clinical research trends. Laboratory validation of defined and candidate biomarkers for both osteoarthritis and osteoporosis is of key importance for future decisional algorithms in the diagnosis, monitoring, and prognosis of these diseases. The current guidelines recommend the use of collagen degradation remnants, eg, CTX-I and CTX-II, in the complementary diagnosis of both osteoporosis and osteoarthritis. Besides the collagen degradation markers, enzymes that regulate bone and articular metabolism are useful in

Beta-blockers and glioma: a systematic review of preclinical studies and clinical results.

Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit angiogenesis and tumor cell proliferation in various cancer types. The aim of this study was to systematically review the evidence on the effect of beta-blockers on glioma growth. A systematic literature search was performed in the PubMed, Embase, Google Scholar, Web of Science, and Cochrane Central to identify all relevant studies. Preclinical studies concerning the pharmacodynamic effects of beta-blockers on glioma growth and prolifer

Chondroprotection and Molecular Mechanism of Action of Phytonutraceuticals on Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease and an important cause of incapacitation. There is a lack of drugs and effective treatments that stop or slow the OA progression. Modern pharmacological treatments, such as analgesics, have analgesic effects but do not affect the course of OA. Long-term use of these drugs can lead to serious side effects. Given the OA nature, it is likely that lifelong treatment will be required to stop or slow its progression. Therefore, there is an urgent need for disease-modifying OA treatments that are also safe for clinical use over long periods. Phytonu