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Fucoidan: An Update on Function, Role in Human Health and Applications.

Fucoidan is a polysaccharide bioactive compound, mainly from brown algae, characterized by multiple biological activities, including anti-inflammatory, anticoagulant, anticancer, antioxidant, antiviral, and cardioprotective properties. In addition, growing scientific evidence supports its epigenetic potential and ability to modulate autophagic mechanisms, two crucial aspects for the treatment and prevention of chronic diseases, such as cancer, inflammation, and aging. For this reason, Fucoidan is a promising candidate for a wide range of applications, both as a bioactive component of drug deli

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… “Fucoidan Protects Mesenchymal Stem Cells Against Oxidative Stress and Enhances Vascular Regeneration in a Murine Hindlimb Ischemia Model.” International Journal of Cardiology 198: 187–195. 10.1016/j.ijcard.2015.06.070. He, R. , Li Y., Han C., Lin R., Qian W., and Hou X.. 2019. …

A novel approach to enhance glioblastoma multiforme treatment efficacy: non-coding RNA targeted therapy and adjuvant approaches.

BackgroundGlioblastoma multiforme (GBM) is a lethal brain tumor. With the current gold standard chemotherapy treatment, temozolomide (TMZ), many patients do not survive beyond one year. While the urgency of researching novel treatments is understandable, the prohibitively high costs and the prolonged duration of research and clinical trials significantly delay the availability of medical advancements to the general public. This highlights the urgent need for adjuvant therapies to enhance treatment effectiveness.Main bodyRecent research has suggested the potential of repurposing FDA-approved dr

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… Disulfiram and NPL4(Bgee database: existing in humans as homology NPLOC4 which expressed mostly in gastrocnemius, apex of heart hindlimb stylopod muscle) siRNA successfully inhibited human renal cell carcinoma (RCC) cell lines 786-o, A498, Caki1, and Caki2 and in xenograft models by potentially quelling …

The Role of Extracellular Vesicles (EVs) in the Epigenetic Regulation of Bone Metabolism and Osteoporosis.

Extracellular vesicles (EVs) are complex phospholipidic structures actively released by cells. EVs are recognized as powerful means of intercellular communication since they contain many signaling molecules (including lipids, proteins, and nucleic acids). In parallel, changes in epigenetic processes can lead to changes in gene function and finally lead to disease onset and progression. Recent breakthroughs have revealed the complex roles of non-coding RNAs (microRNAs (miRNAs) and long non-coding RNAs (lncRNAs)) in epigenetic regulation. Moreover, a substantial body of evidence demonstrates tha

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… LncRNA-H19 Modulates Wnt/β-catenin Signaling by Targeting Dkk4 in Hindlimb Unloaded Rat. Orthop. Surg. 2017;9:319–327. doi: 10.1111/os.12321. 82. Wolf P. The nature and significance of platelet products in human plasma. Br. J. …

Bone Metastasis Pain, from the Bench to the Bedside.

Bone is the most frequent site of metastasis of the most common cancers in men and women. Bone metastasis incidence has been steadily increasing over the years, mainly because of higher life expectancy in oncologic patients. Although bone metastases are sometimes asymptomatic, their consequences are most often devastating, impairing both life quality and expectancy, due to the occurrence of the skeletal-related events, including bone fractures, hypercalcemia and spinal cord compression. Up to 75% of patients endure crippling cancer-induced bone pain (CIBP), against which we have very few weapo

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… This is a device which features 2 scales, that are able to discriminate weight distribution between the 2 hindlimbs, when the animal is stood up at an incline (as visible from A, upper panel). …

Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence.

Mesenchymal stem cells form a population of self-renewing, multipotent cells that can be isolated from several tissues. Multiple preclinical studies have demonstrated that the administration of exogenous MSC could prevent renal injury and could promote renal recovery through a series of complex mechanisms, in particular via immunomodulation of the immune system and release of paracrine factors and microvesicles. Due to their therapeutic potentials, MSC are being evaluated as a possible player in treatment of human kidney disease, and an increasing number of clinical trials to assess the safety

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… In an in vivo mouse model of hindlimb ischemia, clinical and histological analysis revealed that bmMSC and adMSC presented different properties. Therefore, while MSC isolated from various tissue have similar characteristics, further characterization would be beneficial for clinical use. …

Targeting mast cells tryptase in tumor microenvironment: a potential antiangiogenetic strategy.

Angiogenesis is a complex process finely regulated by the balance between angiogenesis stimulators and inhibitors. As a result of proangiogenic factors overexpression, it plays a crucial role in cancer development. Although initially mast cells (MCs) role has been defined in hypersensitivity reactions and in immunity, it has been discovered that MCs have a crucial interplay on the regulatory function between inflammatory and tumor cells through the release of classical proangiogenic factors (e.g., vascular endothelial growth factor) and nonclassical proangiogenic mediators granule-associated (

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… Protease-activated receptor-2 stimulates angiogenesis and accelerates hemodynamic recovery in a mouse model of hindlimb ischemia. Circulation Research. 2002;91(4):346–352. doi: 10.1161/01.res.0000031958.92781.9e. 77. Liu Y, Mueller BM. …

The Herba Patriniae (Caprifoliaceae): A review on traditional uses, phytochemistry, pharmacology and quality control.

ETHNOPHARMACOLOGICAL RELEVANCE: Herba Patriniae has been used for thousands of years in China as a traditional Chinese medicine with heat-clearing and detoxicating effects. It is applied widly for the treatment of rheumatoid arthritis, diarrhea, acute hepatitis, pelvic inflammatory disease and ulcerative colitis in clinic. Two species, namely Patrinia scabiosaefolia Fisch. (PS) and Patrinia villosa Juss. (PV) from the Caprifoliaceae family, are considered as Herba Patriniae in the pharmaceutical industry. AIM OF THE REVIEW: This paper aims to comprehensively outline the traditional uses, bota

Нейронный вклад в управление химически активным балансом: обзор ЭЭГ, ФНИРС, МРТ и ПЕТ.

Справочная информация/задачи: Для предотвращения падений решающее значение имеют быстрые посттуральные реакции, однако нейронные системы, поддерживающие эти ответные действия, не в полной мере понимаются, особенно в том, что касается старения и неврологических расстройств. Понимание того, как мозг обнаруживает, интерпретирует и реагирует на нарушения равновесия, крайне важно для разработки новых мер вмешательства. Цель этого аналитического обзора заключалась в обобщении данных, полученных в ходе исследований нейроимации, с целью выявления кортикальных и субкортических механизмов, лежащих в осн

The role of CD8+ T cells in the immunoregulation of osteoporosis.

INTRODUCTION: Osteoporosis weakens the skeleton by lowering bone mass and damaging bone microarchitecture. A growing body of evidence points to disruptions in osteoimmune homeostasis as a key driver of this disease. In particular, apoptosis of bone cells and immune cells appears to be a critical contributing mechanism. Within the bone marrow, CD8+ T cells display a surprising functional duality: whether they protect bone or promote its loss depends heavily on local signals. Under healthy conditions or after mechanical loading, activated CD8+ T cells help maintain bone mass. They do so mainly b

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… In hindlimb-unloaded mice, CD8 + T cells accumulate in the bone marrow and turn pro-inflammatory: more RANKL, less IFN-γ ( 76 ). This shift partly reflects reduced muscle-derived IL-33, much like in PMOP. Exercise (discussed in 6.1) counteracts this change. …

Current Advances in RNA Therapeutics for Human Diseases.

Following the discovery of nucleic acids by Friedrich Miescher in 1868, DNA and RNA were recognized as the genetic code containing the necessary information for proper cell functioning. In the years following these discoveries, vast knowledge of the seemingly endless roles of RNA have become better understood. Additionally, many new types of RNAs were discovered that seemed to have no coding properties (non-coding RNAs), such as microRNAs (miRNAs). The discovery of these new RNAs created a new avenue for treating various human diseases. However, RNA is relatively unstable and is degraded fairl

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… HIV-based vectors and angiogenesis following rabbit hindlimb ischemia J. Surg. Res. 2005 123 55 66 10.1016/j.jss.2004.06.010 15652951 83. Giacca M. Zacchigna S. VEGF gene therapy: Therapeutic angiogenesis in the clinic and beyond Gene Ther. 2012 19 622 629 10.1038/gt.2012.17 22378343 84. …

The efficacy and applicability of chimeric antigen receptor (CAR) T cell-based regimens for primary bone tumors: A comprehensive review of current evidence.

Primary bone tumors (PBT), although rare, could pose significant mortality and morbidity risks due to their high incidence of lung metastasis. Survival rates of patients with PBTs may vary based on the tumor type, therapeutic interventions, and the time of diagnosis. Despite advances in the management of patients with these tumors over the past four decades, the survival rates seem not to have improved significantly, implicating the need for novel therapeutic interventions. Surgical resection with wide margins, radiotherapy, and systemic chemotherapy are the main lines of treatment for PBTs. N

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… E1, C showed progression of cancer leading to hindlimb amputation at d 100. TI: B7-H3-CAR T cells trafficked to engrafted right tibial tumors on d 3 post implantation and more tibial expansion on the 4th a compared to C(p < 0.01). … E1, C showed progression of cancer leading to hindlimb amputation at d 100. TI: B7-H3-CAR T cells trafficked to engrafted right tibial tumors on d 3 post implantation and more tibial expansion on the 4th a compared to C(p < 0.01). …

Bone sialoprotein: a multifunctional regulator of bone remodelling and tumour progression.

Bone sialoprotein (BSP) is a major non-collagenous protein of the bone extracellular matrix and an important regulator of bone formation and resorption. BSP is produced by bone cells and chondrocytes and present in the bone matrix, cells, dentin and cartilage. However, its aberrant expression in primary tumour tissues and the sera of cancer patients with metastases implicates BSP in tumour biology and progression. The Arg-Gly-Asp (RGD) motif of BSP may be crucial not only for the attachment of metastasising cells to the bone surface but also for tumour growth, survival and activity. This revie

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… Relationship between bone sialoprotein and osteopontin in bone remodelling Models of hindlimb disuse (e.g. tail suspension) induce bone loss in BSP-knockout mice, 100 whereas OPN-knockout mice are protected from such loss, 114 highlighting a pivotal role for OPN in bone resorption under reduced mechanical …

Role of TRP Channels in Cancer-Induced Bone Pain.

The burden of cancer is growing in almost every country. Bone metastases significantly affect the prognosis and lead to an increase in mortality and morbidity. The management of cancer-induced bone pain (CIBP) still shows various unmet needs. Opioid use is burdened by a number of possible side effects. Moreover, recent progresses in cancer treatment significantly increased the life expectancy of cancer patients, even those with metastatic disease. In this narrative review, we reported the main findings regarding TRP channel function in cancer pain models. TRP cation channels play a key role in

Osteosarcoma of the appendicular skeleton in dogs: consensus and guidelines.

Osteosarcoma (OSA) in dogs poses a clinical challenge to veterinary practitioners across the globe. As knowledge evolves, so too do clinical practices. However, there remain uncertainties and controversies. There is value for the veterinary community at large in the generation of a contemporary wide-ranging guideline document. The aim of this project was therefore to assimilate the available published knowledge into a single accessible referenced resource and to provide expert clinical guidance to support professional colleagues as they navigate current OSA challenges and controversies. Primar

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… In humans, appendicular OSA is most commonly found in the femur and tibia; in dogs where the forelimb supports 60% of the dog’s bodyweight, appendicular OSA is found twice as often in the forelimb (proximal humerus and distal radius) than the hindlimb (distal femur and proximal and distal tibia) [( 2 …

Epigenetic mechanisms in cardiovascular complications of diabetes: towards future therapies.

The pathophysiological mechanisms of cardiovascular disease and microvascular complications in diabetes have been extensively studied, but effective methods of prevention and treatment are still lacking. In recent years, DNA methylation, histone modifications, and non-coding RNAs have arisen as possible mechanisms involved in the development, maintenance, and progression of micro- and macro-vascular complications of diabetes. Epigenetic changes have the characteristic of being heritable or deletable. For this reason, they are now being studied as a therapeutic target for the treatment of diabe

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… Notably, Mohammed et al. demonstrated in a mouse model of diabetes that apabetalone is able to prevent maladaptive transcriptional programmed in ECs, thereby preserving angiogenic properties and post-ischemic vascularization after hindlimb ischemia (Mohammed et al. 2022 ). …

Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1.

The lysosomal storage disorders Niemann-Pick disease Type C1 (NPC1) and Type C2 (NPC2) are rare diseases caused by mutations in the NPC1 or NPC2 gene. Both NPC1 and NPC2 are proteins responsible for the exit of cholesterol from late endosomes and lysosomes (LE/LY). Consequently, mutations in one of the two proteins lead to the accumulation of unesterified cholesterol and glycosphingolipids in LE/LY, displaying a disease hallmark. A total of 95% of cases are due to a deficiency of NPC1 and only 5% are caused by NPC2 deficiency. Clinical manifestations include neurological symptoms and systemic

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… It is characterized by progressive weight loss, loss of motor coordination, ataxia, tremors, hindlimb paralysis, and decreased lifespan [ 17 , 18 ]. …

Терапевтический потенциал зубных мезенхимальных стволовых клеток в сравнении с мезенхимальными стволовыми клетками из других источников: систематический обзор исследований животных.

ЦЕНТРАЛЬНАЯ терапия на основе стволовых клеток, являющаяся одной из важнейших областей регенеративной медицины, направлена на совершенствование механизмов ремонта тела (d) путем стимулирования, модуляции и регулирования внутренних стволовых клеток или пополнения пулов клеток, способствуя тем самым развитию гомеостаза и регенерации тканей и предлагая перспективное лечение многочисленных системных заболеваний. В настоящем систематическом обзоре содержится всеобъемлющее резюме исследований животных, в ходе которых изучается эффективность зубоврачебных мезенхимальных стволовых клеток (НКЦ) в лечен

Exosome-mediated repair of spinal cord injury: a promising therapeutic strategy.

Spinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients' quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin w

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… Chen et al. [ 95 ] claimed that FTY720-loaded NSCs-Exos therapy could promote neuronal morphology by modulating the PTEN/AKT pathway and improve hindlimb motor function. SCs-Exos and MG-Exos have protect axons through the EGFR/Akt/mTOR and p53/p21/CDK1 pathways, respectively [ 106 , 154 ]. …

Targeting the CD47-TSP1 Axis in Abdominal Aortic Aneurysm: A Novel Immunotherapeutic Approach.

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disorder characterized by progressive dilation and weakening of the abdominal aortic wall. Despite advances in surgical repair, rupture remains associated with mortality rates exceeding 65%, and no effective pharmacological therapy exists to prevent disease progression. Increasing evidence highlights chronic inflammation, extracellular matrix degradation, and immune dysregulation as central drivers of AAA pathogenesis. Among these mechanisms, the thrombospondin-1 (TSP1)-CD47 signaling axis has emerged as a critical upstream regulat

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… CD47 knockout or blockade has been shown to enhance reperfusion and angiogenesis in ischemic models including hindlimb ischemia and skin flap transplantation in both mice and pigs [ 116 , 121 ]. …

2,4 Dinitrophenol as Medicine.

In the sanctity of pure drug discovery, objective reasoning can become clouded when pursuing ideas that appear unorthodox, but are spot on physiologically. To put this into historical perspective, it was an unorthodox idea in the 1950's to suggest that warfarin, a rat poison, could be repositioned into a breakthrough drug in humans to protect against strokes as a blood thinner. Yet it was approved in 1954 as Coumadin® and has been prescribed to billions of patients as a standard of care. Similarly, no one can forget the horrific effects of thalidomide, prescribed or available without a prescri

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… Under anesthesia, the sciatic nerve was exposed on the left hindlimb and clamped for 1-min. This induces extensive nerve damage by 48-h. Immediately after the trauma, the skin is sutured closed and subjects are administered one dose of 0.06 mg/kg i.p. injection of DNP. …