Modeling the effect of blunt impact on mitochondrial function in cartilage: implications for development of osteoarthritis

Objective Osteoarthritis (OA) is a disease characterized by degeneration of joint cartilage. It is associated with pain and disability and is the result of either age and activity related joint wear or an injury. Non-invasive treatment options are scarce and prevention and early intervention methods are practically non-existent. The modeling effort presented in this article is constructed based on an emerging biological hypothesis—post-impact oxidative stress leads to cartilage cell apoptosis and hence the degeneration observed with the disease. The objective is to quantitatively describe the loss of cell viability and function in cartilage after an injurious impact and identify the key parameters and variables that contribute to this phenomenon. Methods We constructed a system of differential equations that tracks cell viability, mitochondrial function, and concentrations of reactive oxygen species (ROS), adenosine triphosphate (ATP), and glycosaminoglycans (GAG). The system was solved using MATLAB and the equations’ parameters were fit to existing data using a particle swarm algorithm. Results The model fits well the available data for cell viability, ATP production, and GAG content. Local sensitivity analysis shows that the initial amount of ROS is the most important parameter. Discussion The model we constructed is a viable method for producing in silico studies and with a few modifications, and data calibration and validation, may be a powerful predictive tool in the search for a non-invasive treatment for post-traumatic osteoarthritis.

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Updated Costs of Uterine Fibroid Treatments Including Focused Ultrasound Surgery

10.31225/osf.io/r8x7t ◽

2018 ◽

Author(s):

Bijan J. Borah ◽

Elizabeth A. Stewart

Keyword(s):

Magnetic Resonance ◽

Focused Ultrasound ◽

Treatment Options ◽

Uterine Fibroids ◽

Reproductive Age ◽

Invasive Treatment ◽

Ultrasound Surgery ◽

Non Invasive ◽

Focused Ultrasound Surgery ◽

Reproductive Age Women

Uterine leiomyomas (fibroids) affect 20–40% of reproductive age women and are the major indication for hysterectomy. Magnetic Resonance-guided Focused Ultrasound Surgery (MRgFUS) is a new, potentially disruptive, non-invasive and uterine-sparing treatment option that has been shown to yield similar or better clinical outcomes than other uterine-sparing interventions. However, the costs of MRgFUS and other minimally-invasive treatment options have not been studied using US practice data. This study attempts to fill this void. And since uterine fibroids are the first FDA-approved indication for MRgFUS treatment, this study may also have implications for other indications which are now investigational.

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Reversal of Renal Insufficiency in an Aging Cat: A 5-year Multi-Crossover Case Study

The Journal of Science and Medicine ◽

10.37714/josam.v2i2.30 ◽

2020 ◽

Vol 2 (2) ◽

Author(s):

Robert Dennis ◽

John Dennis

Keyword(s):

Palliative Care ◽

Renal Insufficiency ◽

Treatment Options ◽

Low Frequency ◽

Standard Of Care ◽

Omega 3 ◽

Current Standard ◽

Invasive Treatment ◽

Non Invasive ◽

Electro Magnetic

Renal failure is a leading cause of suffering and death in domestic cats, with approximately 1 in 3 cats affected. Current standard-of-care treatment usually involves palliative care, diets restricted in protein and phosphorus, plenty of fluids, and sometimes vitamin D and Omega-3. But even with early detection, which is difficult, treatment options are limited and often are not very effective. Dietary restrictions and palliative care are often the best that can be offered, but the creatinine levels tend to inexorably creep upward toward eventual kidney failure and death. We report the effectiveness of the use of a low-frequency, low-intensity, non-invasive treatment using Pulsed Electro-Magnetic Fields, specifically tuned to inductively generate micro-electric currents in deep tissues (ICES®-PEMF). This report chronicles the return to normal and then reversion to renal insufficiency in a single cat, when ICES®-PEMF was applied, then withheld, then applied again, over three cycles of application and non-application, over a 5-year period. A return to normal creatinine levels, with a subsequent return to renal insufficiency as indicated by loss of control of creatinine, correlated precisely with the application and non-application of ICES®-PEMF. The pattern observed during each cycle was as follows: when applied 2 to 3 times weekly for 20-60 minutes each treatment, creatinine levels declined to normal range within 2-3 months. During periods when treatment was discontinued, creatinine levels began to climb to high levels again. We suggest the further study and potential use of ICES®-PEMF as an effective, inexpensive, safe, non-invasive treatment for feline kidney disease.

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Effects of GH/IGF on the Aging Mitochondria

Cells ◽

10.3390/cells9061384 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1384 ◽

Cited By ~ 1

Author(s):

Sher Bahadur Poudel ◽

Manisha Dixit ◽

Maria Neginskaya ◽

Karthik Nagaraj ◽

Evgeny Pavlov ◽

...

Keyword(s):

Oxidative Stress ◽

Growth Hormone ◽

Cell Differentiation ◽

Growth Factor ◽

Mitochondrial Biogenesis ◽

Mitochondrial Function ◽

Cellular Aging ◽

Mitochondrial Mass ◽

Atp Production ◽

And Function

The mitochondria are key organelles regulating vital processes in the eukaryote cell. A decline in mitochondrial function is one of the hallmarks of aging. Growth hormone (GH) and the insulin-like growth factor-1 (IGF-1) are somatotropic hormones that regulate cellular homeostasis and play significant roles in cell differentiation, function, and survival. In mammals, these hormones peak during puberty and decline gradually during adulthood and aging. Here, we review the evidence that GH and IGF-1 regulate mitochondrial mass and function and contribute to specific processes of cellular aging. Specifically, we discuss the contribution of GH and IGF-1 to mitochondrial biogenesis, respiration and ATP production, oxidative stress, senescence, and apoptosis. Particular emphasis was placed on how these pathways intersect during aging.

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OGT regulates mitochondrial biogenesis and function via diabetes susceptibility gene Pdx1

10.2337/figshare.15831735.v1 ◽

2021 ◽

Author(s):

Ramkumar Mohan ◽

Seokwon Jo ◽

Amber Lockridge ◽

Deborah A. Ferrington ◽

Kevin Murray ◽

...

Keyword(s):

Mitochondrial Function ◽

Susceptibility Gene ◽

Mitochondrial Morphology ◽

Cell Physiology ◽

Β Cells ◽

Β Cell ◽

Atp Production ◽

Glcnac Transferase ◽

And Function

O-GlcNAc transferase (OGT), a nutrient-sensor sensitive to glucose flux, is highly expressed in the pancreas. However, the role of OGT in the mitochondria of β-cells is unexplored. Here, we identified the role of OGT in mitochondrial function in β-cells. Constitutive deletion of OGT (βOGTKO) or inducible ablation in mature β-cells (iβOGTKO) causes distinct effects on mitochondrial morphology and function. Islets from βOGTKO, but not iβOGTKO, mice display swollen mitochondria, reduced glucose-stimulated oxygen consumption rate, ATP production and glycolysis. Alleviating ER stress by genetic deletion of Chop did not rescue the mitochondrial dysfunction in βOGTKO mice. We identified altered islet proteome between βOGTKO and iβOGTKO mice. Pancreatic and duodenal homeobox 1 (Pdx1) was reduced in in βOGTKO islets. Pdx1 over-expression increased insulin content and improved mitochondrial morphology and function in βOGTKO islets. These data underscore the essential role of OGT in regulating β-cell mitochondrial morphology and bioenergetics. In conclusion, OGT couples nutrient signal and mitochondrial function to promote normal β-cell physiology. <br>

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Mitochondria-Cytokine Crosstalk Following Skeletal Muscle Injury and Disuse: A Mini-Review

AJP Cell Physiology ◽

10.1152/ajpcell.00462.2020 ◽

2021 ◽

Author(s):

Anita E. Qualls ◽

W. Michael Southern ◽

Jarrod A. Call

Keyword(s):

Skeletal Muscle ◽

Mitochondrial Function ◽

Muscle Injury ◽

Muscle Injuries ◽

Monocyte Chemoattractant Protein 1 ◽

Skeletal Muscle Injury ◽

Atp Production ◽

Bona Fide ◽

Sense And Respond ◽

And Function

Skeletal muscle mitochondria are highly adaptable, highly dynamic organelles that maintain the functional integrity of the muscle fiber by providing ATP for contraction and cellular homeostasis (e.g., Na+/K+ ATPase). Emerging as early modulators of inflammation, mitochondria sense and respond to cellular stress. Mitochondria communicate with the environment, in part, by release of physical signals called mitochondrial-derived damage-associated molecular patterns (mito-DAMPs) and deviation from routine function (e.g. reduced ATP production, Ca2+ overload). When skeletal muscle is compromised, mitochondria contribute to an acute inflammatory response necessary for myofibril regeneration; however, exhaustive signaling associated with altered or reduced mitochondrial function can be detrimental to muscle outcomes. Here we describe changes in mitochondrial content, structure, and function following skeletal muscle injury and disuse and highlight the influence of mitochondrial-cytokine crosstalk on muscle regeneration and recovery. While the appropriate therapeutic modulation following muscle stressors remains unknown, retrospective gene expression analysis reveal interleukin-6 (IL-6), interleukin-1b (IL-1b), chemokine C-X-C motif ligand 1 (CXCL1), and monocyte chemoattractant protein 1 (MCP-1) are significantly upregulated following three unique muscle injuries. These cytokines modulate mitochondrial function and execute bona fide pleiotropic roles that can aid functional recovery of muscle; however, when aberrant, chronically disrupt healing partly by exacerbating mitochondrial dysfunction. Multidisciplinary efforts to delineate the opposing regulatory roles of inflammatory cytokines in the muscle-mitochondrial environment are required to modulate regenerative behavior following skeletal muscle injury or disuse. Future therapeutic directions to consider include quenching or limited release of mito-DAMPs and cytokines present in cytosol or circulation.

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Non-Invasive Treatment of Adolescent Idiopathic Scoliosis: Systematic Literature Review by Using Citation Network Analysis

10.31487/j.ssg.2020.01.01 ◽

2020 ◽

pp. 1-9

Author(s):

Joanne Yip ◽

Jason Pui-Yin Cheung ◽

Joanne Yip ◽

Kenneth Man-Chee Cheung ◽

Kenny YatHong Kwan ◽

...

Keyword(s):

Network Analysis ◽

Literature Review ◽

Treatment Options ◽

Citation Network ◽

Nonsurgical Treatment ◽

Spinal Curvature ◽

Invasive Treatment ◽

Noninvasive Treatment ◽

Non Invasive ◽

Citation Network Analysis

There are many nonsurgical treatment options from adolescent idiopathic scoliosis (AIS) to control the progression of the spinal curvature. However, the existing studies are so diverse and diffuse that it is challenging to find potential trends for further studies without a more comprehensive review in place for reference purposes. Thus, the objective of this review article is to conduct a systematic literature review on the noninvasive treatment of AIS with a citation network analysis. The Web of Science (WoS) was searched using 9 reference keywords to collect published articles in English on nonsurgical treatment options for AIS from 1979 to 2019. Each eligible article focused on the nonsurgical options for treating AIS. In addition, the HistCite and the UCINet softwares were referred to for article distribution and citation network analysis. Only non-invasive treatment options of AIS were included. Studies that estimated the amount of spinal curvature, causes of or risk factors for AIS and any invasive treatments, such as surgery, were not focused on. The articles were independently extracted by 3 authors based on the predefined eligibility criteria. The title, authors, year of publication, country or region of publication, reference list, keywords and other bibliographic information from each article was extracted and analyzed purely based on the data with the HistCite and UCINet programs. At last, a total of 146 articles out of 1594 articles were selected for the literature review after the exclusion of 1357 irrelevant articles and 91 inappropriate studies, such as letters and proceedings papers. Of these 146 articles, the majority were empirical studies (74.0%). There was also a lack of meta-analyses in this research field. Based on the results of the citation network analysis, most of the top 10 articles with the highest local citation scores (LCSs) focused on bracing as a treatment. The popularity of bracing as a research topic was also supported by the citation network structure, as brace treatment was in the largest of the five research clusters; this cluster also included posture training through exercise, managing the corrective forces of braces, 3D analysis of braces and quality of life during brace treatment. However, most of these studies focused on rigid braces. A few studies on non-rigid braces and other types of nonsurgical treatment were available in the current literature, which might indicate potential research areas for future studies. To conclude, noninvasive treatment for AIS has been on the academic radar recently; but there are still research gaps, such as the lack of research on semi-rigid and flexible braces or posture training exercises with biofeedback systems. Further studies could explore these research directions.

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Non-invasive versus invasive treatment options for challenging and progressive infundibulitis

The American Journal of Medicine ◽

10.1016/j.amjmed.2021.10.031 ◽

2021 ◽

Author(s):

Jan P. Nieke ◽

Maria I. Vargas ◽

Patrick Meyer ◽

Jörg D. Seebach ◽

Peter Jandus

Keyword(s):

Treatment Options ◽

Invasive Treatment ◽

Non Invasive

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Influence of Vanadium 4+ and 5+ Ions on the Differentiation and Activation of Human Osteoclasts

International Journal of Biomaterials ◽

10.1155/2017/9439036 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Matthias A. König ◽

Oliver P. Gautschi ◽

Hans-Peter Simmen ◽

Luis Filgueira ◽

Dieter Cadosch

Keyword(s):

Cell Viability ◽

Treatment Options ◽

Implant Failure ◽

Tartrate Resistant Acid Phosphatase ◽

Negative Effects ◽

Cell Viability Assay ◽

Viability Assay ◽

Multinucleated Cells ◽

And Function

Background. In the pathophysiology of implant failure, metal ions and inflammation-driven osteoclasts (OC) play a crucial role. The aim of this study was to investigate whether vanadium (V) ions induce differentiation of monocytic OC precursors into osteoresorptive multinucleated cells. In addition, the influence of V ions on the activation and function of in vitro generated OC was observed. Methods. Human monocytes and osteoclasts were isolated from peripheral blood monocytic cells (PBMCs). Exposition with increasing concentrations (0–3 μM) of V4+/V5+ ions for 7 days followed. Assessment of OC differentiation, cell viability, and resorptional ability was performed by standard colorimetric cell viability assay 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenil)-2H-tetrazolium (MTS), tartrate-resistant acid phosphatase (TRAP) expression, and functional resorption assays on bone slides during a period of 21 days. Results. No significant differences were noted between V4+/V5+ ions (p>0.05). MTS showed significant reduction in cellular viability by V concentrations above 3 μM (p<0.05). V concentrations above 0.5 μM showed negative effects on OC activation/differentiation. Higher V concentrations showed negative effects on resorptive function (all p<0.05) without affecting cell viability. V4+/V5+ concentrations below 3 μM have negative effects on OC differentiation/function without affecting cell survival. Conclusion. Vanadium-containing implants may reduce implant failure rate by influencing osteoclast activity at the bone-implant interface. V-ligand complexes might offer new treatment options by accumulating in the bone.

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Dipeptidyl Peptidase-4 Involved in Regulating Mitochondria Function in Cardiomyocytes through Nrf2 and PGC-1α Signaling

10.21203/rs.3.rs-30722/v1 ◽

2020 ◽

Author(s):

Shih-Yi Lee ◽

Shao-Tung Wu ◽

Ming-Jai Su ◽

Yao-Jen Liang ◽

Hui-Chun Ku

Keyword(s):

Oxidative Stress ◽

Cell Viability ◽

Mitochondrial Function ◽

Dipeptidyl Peptidase ◽

Atp Production ◽

Dipeptidyl Peptidase 4 ◽

Transmembrane Glycoprotein ◽

Mitochondrial Ros ◽

Intracellular Ros ◽

Dependent Pathway

Abstract Background: Oxidative stress is an imbalance between the production of reactive oxygen species (ROS) and the detoxification ability of reactive intermediates. It will lead to mitochondrial damage and dysfunction, resulting in the dysfunction of bioenergetic control and loss of ATP production, which is contributed to the pathogenesis of cardiac diseases. Dipeptidyl peptidase-4 (DPP4) is a transmembrane glycoprotein ubiquitously expressed and has multifunctional properties. DPP4 inhibitors are a class of oral diabetes drugs that inhibit the enzyme activity. In addition to its enzymatic property, considerably less is known regarding the nonenzymatic function of DPP4.Methods: We knocked down DPP4 gene expression in cultured cardiomyocytes to exclude any external and enzymatic substrate effects and compared the response between DPP4 knockdown and wild-type cardiomyocytes in response to oxidative stress.Results: H2O2-induced oxidative stress-stimulated intracellular and mitochondrial ROS concentration led to the loss of mitochondrial function, ATP production, and increased Bax and cleaved PARP expression, resulting in the loss of cell viability in cardiomyocytes. Oxidative stress induced DPP4 expression. Knocking down DPP4 ameliorated H2O2-induced loss of cell viability by preserving mitochondrial bioenergy, reducing intracellular ROS production, alleviating apoptosis-associated protein expression. Knocking down DPP4 increased its capability against oxidative stress by enhancing Nrf2 and PGC-1α signaling, which is associated with preserving mitochondrial function.Conclusions: DPP4 is a mediator of oxidative stress. Knocking down DPP4 without any external substrate mediators increased the capability of cardiomyocytes against oxidative stress, which indicated that DPP4 mediated more than the enzymatic-dependent pathway.

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