Mitochondrial dysfunction is an underlying pathology in numerous diseases. Delivery of diagnostic and therapeutic cargo directly into mitochondria is a powerful approach to study and treat these ...diseases. The triphenylphosphonium (TPP+) moiety is the most widely used mitochondriotropic carrier. However, studies have shown that TPP+ is not inert; TPP+ conjugates uncouple mitochondrial oxidative phosphorylation. To date, all efforts toward addressing this problem have focused on modifying lipophilicity of TPP+-linker-cargo conjugates to alter mitochondrial uptake, albeit with limited success. We show that structural modifications to the TPP+ phenyl rings that decrease electron density on the phosphorus atom can abrogate uncoupling activity as compared to the parent TPP+ moiety and prevent dissipation of mitochondrial membrane potential. These alterations of the TPP+ structure do not negatively affect the delivery of cargo to mitochondria. Results here identify the 4-CF3-phenyl TPP+ moiety as an inert mitochondria-targeting carrier to safely target pharmacophores and probes to mitochondria.
Generation of mitochondrial reactive oxygen species (ROS) is an important process in triggering cellular necrosis and tissue infarction during ischemia-reperfusion (IR) injury. Ischemia results in ...accumulation of the metabolite succinate. Rapid oxidation of this succinate by mitochondrial complex II (Cx-II) during reperfusion reduces the co-enzyme Q (Co-Q) pool, thereby driving electrons backward into complex-I (Cx-I), a process known as reverse electron transport (RET), which is thought to be a major source of ROS. During ischemia, enhanced glycolysis results in an acidic cellular pH at the onset of reperfusion. While the process of RsET within Cx-I is known to be enhanced by a high mitochondrial trans-membrane ΔpH, the impact of pH itself on the integrated process of Cx-II to Cx-I RET has not been fully studied. Using isolated mouse heart and liver mitochondria under conditions which mimic the onset of reperfusion (i.e., high ADP), we show that mitochondrial respiration (state 2 and state 3) as well as isolated Cx-II activity are impaired at acidic pH, whereas the overall generation of ROS by Cx-II to Cx-I RET was insensitive to pH. Together these data indicate that the acceleration of Cx-I RET ROS by ΔpH appears to be cancelled out by the impact of pH on the source of electrons, i.e. Cx-II. Implications for the role of Cx-II to Cx-I RET derived ROS in IR injury are discussed.
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•ROS from complex I (Cx-I) reverse electron transport (RET) is enhanced at acidic pH.•Mitochondrial complex II (Cx-II) activity is inhibited at acidic pH.•These effects cancel out, yielding no net pH response of Cx-II to Cx-I RET ROS.
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BSTRACT
Physical rehabilitation is evolving day by day. In the same way, simulation in rehabilitation is increasing and has now become a cornerstone for rehabilitation programs. Increase in the ...number of new protocols, clinical methods, and treatment standardization, virtual reality is appearing as a new medium to deliver the simulation. Virtual reality gives the benefits of forming standardized treatment protocols on demand for various conditions repetitively with a cost-effective delivery system. This was an observational retrospective study. The PubMed database was used to obtain the available material related to virtual reality and rehabilitation and was searched using the same keywords. The articles were then sorted as the subject to the recent decade. The basic information was then obtained, which included timespan, sources of the document, average years of publication, document types we collected, and average citation per year per document. Analysis of the literature that was available online related to virtual reality and rehabilitation between 2011 and 2021 generated a list of 813 documents from 275 sources, of which 810 were from journal articles and 3 were book chapters with an average year of publication of 2.16. The highest number of publications was 480 in 2020, followed by 150 in 2019, 95 in 2018, and 28 in 2017. The annual growth rate percentage of scientific publications was 26.1%. Therefore, more studies should be performed on virtual reality.
Type 2 diabetes is associated with insulin resistance, impaired pancreatic β-cell insulin secretion, and nonalcoholic fatty liver disease. Tissue-specific SWELL1 ablation impairs insulin signaling in ...adipose, skeletal muscle, and endothelium, and impairs β-cell insulin secretion and glycemic control. Here, we show that I
and SWELL1 protein are reduced in adipose and β-cells in murine and human diabetes. Combining cryo-electron microscopy, molecular docking, medicinal chemistry, and functional studies, we define a structure activity relationship to rationally-design active derivatives of a SWELL1 channel inhibitor (DCPIB/SN-401), that bind the SWELL1 hexameric complex, restore SWELL1 protein, plasma membrane trafficking, signaling, glycemic control and islet insulin secretion via SWELL1-dependent mechanisms. In vivo, SN-401 restores glycemic control, reduces hepatic steatosis/injury, improves insulin-sensitivity and insulin secretion in murine diabetes. These findings demonstrate that SWELL1 channel modulators improve SWELL1-dependent systemic metabolism in Type 2 diabetes, representing a first-in-class therapeutic approach for diabetes and nonalcoholic fatty liver disease.
Alkb homolog 7 (ALKBH7) is a mitochondrial α-ketoglutarate dioxygenase required for DNA alkylation-induced necrosis, but its function and substrates remain unclear. Herein, we show ALKBH7 regulates ...dialdehyde metabolism, which impacts the cardiac response to ischemia-reperfusion (IR) injury. Using a multi-omics approach, we find no evidence ALKBH7 functions as a prolyl-hydroxylase, but we do find
mice have elevated glyoxalase I (GLO-1), a dialdehyde detoxifying enzyme. Metabolic pathways related to the glycolytic by-product methylglyoxal (MGO) are rewired in
mice, along with elevated levels of MGO protein adducts. Despite greater glycative stress, hearts from
mice are protected against IR injury, in a manner blocked by GLO-1 inhibition. Integrating these observations, we propose ALKBH7 regulates glyoxal metabolism, and that protection against necrosis and cardiac IR injury bought on by ALKBH7 deficiency originates from the signaling response to elevated MGO stress.
Temporomandibular joint (TMJ) is a bicondylar joint. Various conditions have the same clinical presentation as TMJ dysfunction, which requires a thorough assessment of active and passive movements ...and palpation of the joints surrounding the joint. Many times, TMJ dysfunction occurs due to an alteration in the cervical spine. The patient complains of clicking or popping sound at the jaw and a reduced maximum mouth opening. The conditions that lead to TMJ dysfunction include bruxism, arthritis, stress, injury to the jaw, and overuse. The trend of the available literature has changed from 1972 to 2021 to assess changing trends in the publication on TMJ about authors, country, collaboration of the institutes, and the journal. We have done this bibliometric assessment. The articles were collected from the PubMed database; the keywords used were temporomandibular dysfunction (TMD), neck pain, physiotherapy, and rehabilitation. A total of 437 articles were found from 1975 to 2021, which were then converted into pictorial forms using the CiteSapce R software, and the data were interpreted. The analysis of the bibliometrics of publications on TMD, neck pain, and functional disability between the years 1975 and 2021 shows a total of 437 articles were published. The articles were from 196 sources; the highest number of publications were seen from 2014 until 2021, with the highest number of published papers by author Yoo WG and the highest number of articles published by the Journal of Physical Therapy Science. This bibliometric analysis depicts that the quantity of literature on TMD and the forward head has increased, as has the effectiveness of physical therapy interventions on the forward head in terms of correcting temporomandibular dysfunction.
Fractures of the parasymphysis occur in 15% of all cases of mandibular fracture. The mandible occupies the lowest portion of the face. The prominent bone of the face is severely injured when the ...lower face is hit by high impacts with upward or obliquely directed force. In this case study, we discussed the alleged trauma case of a 20-year-old man who fell from a height on August 27, 2022, at about 9:00 p.m. near Wardha. His family took him to the hospital in Wardha due to pain that was aggravated during chewing and swelling in his jaw. On investigation, an X-ray was done, and a left parasymphysis and right-side body fracture were noticed. Later, the patient underwent surgery, where open reduction and internal fixation of the left parasymphysis and the right-side body fracture with plating and intermaxillary fixation (IMF) were done. Then he was referred to the physiotherapy department for therapeutic intervention. Rehabilitation was given to reduce pain and swelling, regain full range of motion, gradually increase mobility, and keep associated muscles strong. A six-week protocol was administered to the patient. It was found that the therapeutic approach was quite effective for the patient.
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Structural studies of topoisomerase-fluoroquinolone-DNA ternary complexes revealed a cavity between the quinolone N-1 position and the active site tyrosine. Fluoroquinolone ...derivatives having positively charged or aromatic moieties extended from the N-1 position were designed to probe for binding contacts with the phosphotyrosine residue in ternary complex. While alkylamine, alkylphthalimide, and alkylphenyl groups introduced at the N-1 position afforded derivatives that maintained modest inhibition of the supercoiling activity of DNA gyrase, none retained ability to poison DNA gyrase. Thus, the addition of a large and/or long moiety at the N-1 position disrupts ternary complex formation, and retained ability to inhibit supercoiling is likely through interference with the strand breakage reaction. Two derivatives were found to possess inhibitory effects on the decatenation activity of human topoisomerase II.
Introduction Dance movement therapy (DMT) is a movement-based psychosocial intervention that incorporates the therapeutic components of dance movements and group psychotherapy. DMT, also known as ...creative movement therapy (CMT) is a psychotherapy used as a complementary therapy in cancer care. It helps in enhancing mood, emotions, self-expression and helps to rebuild self-confidence. Besides, it allows the patients to recognise their own strengths and weaknesses as well as helps to improve physical capabilities. Methods By simple random sampling method, 30 breast cancer patients were recruited at Pravara Rural Hospital, Loni, Maharashtra, India. The participants were in the age range of 30-60 years based on the inclusion and exclusion criteria. Pre-intervention scores of cancer-related fatigue (CRF) were taken using the Brief Fatigue Inventory (BFI) scale and intervention was given for 45 minutes each day for 5 days a week, over a span of 2 weeks. Thereafter, post-intervention assessment was done and the scores were noted. Pre-intervention and post-intervention scores were compared using paired t-test. Results The mean and standard deviation (SD) of pre- and post-BFI scores derived by using paired t-test was 73.76 (8.6) and 69.33 (9.8), respectively, with a p-value of < 0.001, which is highly significant. Conclusion The results of the present study revealed that DMT seems to be effective in reducing some amount of CRF in breast cancer patients undergoing radiation therapy. Besides, it turned out to be an engaging, entertaining and cost-effective approach. The investigation showed that DMT appears to be beneficial in reducing the side effects of radiation therapy such as pain, stress, anxiety and fear, giving a psychotherapeutic relief but did not completely remove the persistent fatigue experienced by the breast cancer patients. Thus, further investigation with long-term follow-up is recommended.
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