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Xenograft of Human Umbilical Mesenchymal Stem Cells from Wharton's Jelly Differentiating into Osteocytes and Reducing Osteoclast Activity Reverses Osteoporosis in Ovariectomized Rats.

We examined the effects of human umbilical cord-derived mesenchymal stem cells (HUMSCs) in Wharton's jelly on ovariectomy (OVX)-induced osteoporosis by using in vitro and in vivo experiments. Two months after OVX, the rats gained weight and had a decreased serum estradiol level . Both micro-computed tomography (micro-CT) and histochemical analyses revealed a marked decrease in the bone volume (BV) and collagen content within the head, neck, and distal condyle of the femur, indicating that the osteoporosis animal model was successfully established 2 mo after bilateral OVX. Subsequently, 2.5 × 1

Targeting of multiple myeloma-related angiogenesis by miR-199a-5p mimics: in vitro and in vivo anti-tumor activity.

Multiple myeloma (MM) cells induce relevant angiogenic effects within the human bone marrow milieu (huBMM) by the aberrant expression of angiogenic factors. Hypoxia triggers angiogenic events within the huBMM and the transcription factor hypoxia-inducible factor-1α (HIF-1α) is over-expressed by MM cells. Since synthetic miR-199a-5p mimics negatively regulates HIF-1α, we here investigated a miRNA-based therapeutic strategy against hypoxic MM cells. We indeed found that enforced expression of miR-199a-5p led to down-modulated expression of HIF-1α as well as of other pro-angiogenic factors such a

Glucocorticoids-based prodrug design: Current strategies and research progress.

Attributing to their broad pharmacological effects encompassing anti-inflammation, antitoxin, and immunosuppression, glucocorticoids (GCs) are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus, nephritis, arthritis, ulcerative colitis, asthma, keratitis, macular edema, and leukemia. However, long-term use often causes undesirable side effects, including metabolic disorders-induced Cushing's syndrome (buffalo back, full moon face, hyperglycemia, etc.), osteoporosis, aggravated infection, psychosis, glaucoma, and cataract. These notorious side e

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… GCs have been reported to expand the nuclear pore and translocate into the nucleus upon binding with GRs, thereby facilitating DNA transport into the nucleus. … It is reported that the receptor enlarges the nuclear pore to 60 nm during the translocation process, which facilitates the translocation of the polymer/DNA complex into the nucleus [ 99 , 100 ]. …

Physiological functions and pharmacological targeting of transient receptor potential channels.

Transient receptor potential (TRP) channels represent an extensive and diverse protein family fulfilling salient roles as versatile cellular sensors and effectors. The pivotal role of TRP and related ion channels in sensory processes has been well documented. Over the last few years, a new concept has emerged that TRP proteins control an exceptionally broad spectrum of homeostatic physiological functions such as maintenance of body temperature, blood pressure, transmitter release from neurons, mineral and energy homeostasis, and reproduction. This notion is further supported by more than 20 he

Proceedings of International Conference on Cell Death in Cancer and Toxicology. February 20-22, 2018. Guest Editors: Kausar M. Ansari, CSIR-IITR, India and Dhyan Chandra, Roswell Park, USA.

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The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.

The cGAS-STING pathway acts as a critical molecular hub connecting genomic instability with cellular senescence. Functioning as a key regulator of the innate immune system, this pathway detects aberrant cytoplasmic DNA to activate downstream inflammatory responses, thereby playing a pivotal role in aging-related diseases. This review systematically explores the core mechanisms by which the cGAS-STING pathway regulates cellular senescence, emphasizing its role in triggering senescence through the recognition of DNA damage signals (e.g., oxidative stress, telomere dysfunction) and promoting para

Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.

Reactive oxygen species (ROS) act as critical secondary messengers in various intracellular signaling pathways that regulate cellular proliferation, differentiation, and survival under normal physiological conditions. However, dysregulation of redox signaling-driven by genetic mutations, epigenetic alterations, and posttranscriptional or posttranslational modifications-plays a central role in malignant transformation and cancer progression. Cancer cells typically exhibit elevated basal ROS levels due to increased metabolic activity, mitochondrial dysfunction, and oncogene activation. This mode

Molecular Classification and Overcoming Therapy Resistance for Acute Myeloid Leukemia with Adverse Genetic Factors.

The European LeukemiaNet (ELN) criteria define the adverse genetic factors of acute myeloid leukemia (AML). AML with adverse genetic factors uniformly shows resistance to standard chemotherapy and is associated with poor prognosis. Here, we focus on the biological background and real-world etiology of these adverse genetic factors and then describe a strategy to overcome the clinical disadvantages in terms of targeting pivotal molecular mechanisms. Different adverse genetic factors often rely on common pathways. KMT2A rearrangement, DEK-NUP214 fusion, and NPM1 mutation are associated with the

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… The NUP214 protein, also known as CAN, is a component of the nuclear pore complex and plays an important role in the nucleocytoplasmic transport of macromolecules [ 13 , 14 ]. … The Human Homologue of Yeast CRM1 Is in a Dynamic Subcomplex with CAN/Nup214 and a Novel Nuclear Pore Component Nup88. EMBO J. 1997;16:807–816. doi: 10.1093/emboj/16.4.807. 14. …

Insights into platinum-induced peripheral neuropathy-current perspective.

Cancer is a global health problem that is often successfully addressed by therapy, with cancer survivors increasing in numbers and living longer world around. Although new cancer treatment options are continuously explored, platinum based chemotherapy agents remain in use due to their efficiency and availability. Unfortunately, all cancer therapies affect normal tissues as well as cancer, and more than 40 specific side effects of platinum based drugs documented so far decrease the quality of life of cancer survivors. Chemotherapy-induced peripheral neuropathy is a frequent side effects of plat

Novel intriguing strategies attenuating to sarcopenia.

Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, increased risk of fall-related injury, and, often, frailty. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. Resistance training combined with amino acid-containing supplements is often utilized to pre

Нейтрофилы, НЕТ и множественный склероз: мини-обзор.

Множественный склероз (MS), хроническое аутоиммунное и дегенеративное заболевание, характеризующееся активацией различных провокационных клеток, приводит к обезвоживанию и нейрональным травмам. Нейтрофилы, которые часто недооцениваются в MS, получают все большее внимание за свои важные функции у пациентов MS и экспериментальную аутоиммунную энцефаломиелитную модель (EAE). Нейтрофилы играют многообразную роль в посредничестве патогенеза аутоиммунных заболеваний, и многочисленные исследования свидетельствуют о том, что нейтрофилы могут играть решающую роль благодаря образованию нейтрофильной вне

Hyaluronan (HA) interacting proteins RHAMM and hyaluronidase impact prostate cancer cell behavior and invadopodia formation in 3D HA-based hydrogels.

To study the individual functions of hyaluronan interacting proteins in prostate cancer (PCa) motility through connective tissues, we developed a novel three-dimensional (3D) hyaluronic acid (HA) hydrogel assay that provides a flexible, quantifiable, and physiologically relevant alternative to current methods. Invasion in this system reflects the prevalence of HA in connective tissues and its role in the promotion of cancer cell motility and tissue invasion, making the system ideal to study invasion through bone marrow or other HA-rich connective tissues. The bio-compatible cross-linking proce

HDACs and Their Inhibitors on Post-Translational Modifications: The Regulation of Cardiovascular Disease.

Cardiovascular diseases (CVD), such as myocardial hypertrophy, heart failure, atherosclerosis, and myocardial ischemia/reperfusion (I/R) injury, are among the major threats to human health worldwide. Post-translational modifications alter the function of proteins through dynamic chemical modification after synthesis. This mechanism not only plays an important role in maintaining homeostasis and plays a crucial role in maintaining normal cardiovascular function, but is also closely related to the pathological state of various diseases. Histone deacetylases (HDACs) play an important role in the

Novel Therapeutics for Anthracycline Induced Cardiotoxicity.

Anthracyclines remain an essential component of the treatment of many hematologic and solid organ malignancies, but has important implications on cardiovascular disease. Anthracycline induced cardiotoxicity (AIC) ranges from asymptomatic LV dysfunction to highly morbid end- stage heart failure. As cancer survivorship improves, the detection and treatment of AIC becomes more crucial to improve patient outcomes. Current treatment modalities for AIC have been largely extrapolated from treatment of conventional heart failure, but developing effective therapies specific to AIC is an area of growing

Early Application of High Cut-Off Haemodialysis for de-Novo Myeloma Nephropathy is Associated with Long-Term Dialysis-Independency and Renal Recovery.

BackgroundMultiple myeloma (MM) is a haematological malignancy associated with kidney injury resulting from cast nephropathy, which can be caused by monoclonal free light chains (FLC). It has been demonstrated that early reduction of FLC can lead to a higher proportion of patients recovering renal function with a better outcome, especially if high cut-off haemodialysis (HCO-HD) combined with chemotherapy is used.Patients and methodsIn this study, four cases with MM nephropathy were treated with HCO-HD and chemotherapy at a single institution during the period from August 2009 to August 2011. A

Нанотехнология в области гематологии: усиление терапевтической эффективности с помощью нанопчастей.

Фон и цели Гематологические заболевания, такие, как лейкемия, лимфома и множественная миелома, вносят значительный вклад в глобальный диагноз рака. Несмотря на прогресс в традиционных методах лечения, таких, как химиотерапия и иммунотерапия, эти методы лечения сталкиваются с ограничениями, включая неконкретную адресность, побочные эффекты и резистентность к лекарствам. Цель этого обзора заключается в изучении потенциала нанотехнологии, в частности наночастиц (НФ), для улучшения терапевтических последствий для этих раковых заболеваний путем расширения поставок наркотиков и снижения токсичности.

Selinexor in relapsed/refractory multiple myeloma.

Multiple myeloma (MM) represents an incurable hematologic malignancy. Despite significant advances over the past decade, with the advent of multiple new classes of anti-myeloma agents, including immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies, patients ultimately relapse. Selinexor is a first-in-class exportin-1 inhibitor with activity in these multiply relapsed and refractory patients. Although the current Food and Drug Administration (FDA) approval is for the doublet of Selinexor in combination with dexamethasone, ongoing clinical trials are evaluating a number of com

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… IMP, importin; NPC, nuclear pore complex; XPO1, exportin 1. Preclinical Exportin-1 (XPO1) is overexpressed in a large variety of malignancies, including MM, as well as in a variety of solid and liquid tumors. …

Review on Bortezomib Resistance in Multiple Myeloma and Potential Role of Emerging Technologies.

Multiple myeloma is a hematological cancer type. For its treatment, Bortezomib has been widely used. However, drug resistance to this effective chemotherapeutic has been developed for various reasons. 2D cell cultures and animal models have failed to understand the MM disease and Bortezomib resistance. It is therefore essential to utilize new technologies to reveal a complete molecular profile of the disease. In this review, we in-depth examined the possible molecular mechanisms that cause Bortezomib resistance and specifically addressed MM and Bortezomib resistance. Moreover, we also included

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… Vaults are ribonucleoprotein particles comprising RNA and protein and are found in the cytoplasm as a fraction of the nuclear membrane and nuclear pore complex [ 66 ]. Thus, they contribute to drug resistance by transporting substances between the nucleus and cytoplasm. …

Emerging Mechanisms and Treatment Progress on Liver Metastasis of Colorectal Cancer.

Colorectal cancer is currently the third largest malignant tumor in the world, with high new cases and high mortality. Metastasis is one of the most common causes of death of colorectal cancer, of which liver metastasis is the most fatal. Since the beginning of the Human Genome Project in 2001, people have gradually recognized the 3 billion base pairs that make up the human genome, of which only about 1.5% of the nucleic acid sequences are used for protein coding, including proto-oncogenes and tumor suppressor genes. A large number of differences in the expression of proto-oncogenes and tumor

Unlocking the therapeutic potential of cellular mechanobiology.

Mechanobiology is a rapidly advancing field at the intersection of biology, physics, and engineering that reveals how mechanical forces shape cellular behavior, tissue architecture, and disease progression. By elucidating how cells sense and transduce mechanical cues, mechanobiology has fundamentally advanced our understanding of processes ranging from migration and differentiation to immune responses and tissue remodeling. These advances have driven the development of innovative biophysical tools and engineered biomaterials that enable precise modulation of the cellular microenvironment. Tran

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… At the nuclear level, curvature induces shape deformations that influence gene expression: Nuclei are compressed vertically at convex interfaces, which can alter nuclear pore organization and the localization of mechanosensitive transcriptional regulators, while concave regions relieve mechanical constraints …