The Effects of Photobiomodulation on Knee Function, Pain, and Exercise Tolerance in Older Adults: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To assess whether photobiomodulation therapy (PBMT) enhances the benefits of exercise in older adults. DATA SOURCES: PubMed, Scopus, Medline, and Web of Science, dated to February 2023. STUDY SELECTION: All included studies were randomized controlled trials of PBMT combined with exercise co-intervention in persons 60 years and older. OUTCOME MEASURES: Western Ontario and McMaster University Osteoarthritis Index (WOMAC-total, pain, stiffness and function), perceived pain intensity, timed Up and Go (TUG) Test, 6-min walk test (6MWT), muscle strength, and knee range of motion were included. DATA EXTRACTION: Two researchers independently performed data extraction. Article data were extracted in Excel and summarized by a third researcher. DATA SYNTHESIS: The meta-analysis included 14 of the 1864 studies searched in the database. No statistical differences were found between the treatment and control groups in terms of WOMAC-stiffness (mean difference [MD]=-0.31, 95% confidence interval [CI] -0.64 to 0.03), TUG (MD=-0.17, 95% CI -0.71 to 0.38), 6MWT (MD=32.2, 95% CI -44.62 to 109.01), or muscle strength (standardized mean difference=0.24, 95% CI -0.02 to 0.50). However, statistically significant differences were found for WOMAC-total (MD=-6.83, 95% CI -12.3 to -1.37), WOMAC-pain (MD=-2.03, 95% CI -4.06 to -0.01), WOMAC-function (MD=-5.03, 95% CI -9.11 to -0.96), visual analog scale/numeric pain rating scale (MD=-1.24, 95% CI -2.43 to -0.06), and knee range of motion (MD=1.47, 95% CI 0.07 to 2.88). CONCLUSIONS: In older adults who exercise regularly, PBMT can potentially provide additional pain relief, improve knee joint function, and increase knee joint range of motion.

Age-related changes in adipose tissue metabolomics and inflammation, cardiolipin metabolism, and ferroptosis markers in female aged rat model.

Aging adipose tissue exhibits elevated inflammation and oxidative stress that are major sources of age-related metabolic dysfunction. However, the exact metabolic changes associated with inflammation and oxidative stress are unclear. To address this topic, we assessed variation in metabolic phenotypes of adipose tissue from 18 months adult sedentary (ASED), 26 months old sedentary (OSED), and 8 months young sedentary (YSED). The results of metabolomic analysis showed that ASED and OSED group had higher palmitic acid, elaidic acid, 1-heptadecanol, and α-tocopherol levels than YSED, but lower sarcosine levels. Furthermore, stearic acid was specifically elevated in ASED compared with YSED. Cholesterol was upregulated specifically in the OSED group compared with YSED, whereas linoleic acid was downregulated. In addition, ASED and OSED had more inflammatory cytokines, lower antioxidant capacity, and higher expression of ferroptosis-related genes than YSED. Moreover, mitochondrial dysfunction associated with abnormal cardiolipin synthesis was more pronounced in the OSED group. In conclusion, both ASED and OSED can affect the FA metabolism and increase oxidative stress in adipose tissue, leading to inflammation. In particular, linoleic acid content specifically decreases in OSED, which associated with abnormal cardiolipin synthesis and mitochondrial dysfunction in adipose tissue.

Long-term detraining reverses the improvement of lifelong exercise on skeletal muscle ferroptosis and inflammation in aging rats: fiber-type dependence of the Keap1/Nrf2 pathway.

We investigated the effects of lifelong aerobic exercise and 8 months of detraining after 10 months of aerobic training on circulation, skeletal muscle oxidative stress, and inflammation in aging rats. Sprague-Dawley rats were randomly assigned to the control (CON), detraining (DET), and lifelong aerobic training (LAT) groups. The DET and LAT groups began aerobic treadmill exercise at the age of 8 months and stopped training at the 18th and 26th month, respectively; all rats were sacrificed when aged 26 months. Compared with CON, LAT remarkably decreased serum and aged skeletal muscle 4-hydroxynonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. Superoxide dismutase 2(SOD2) levels were higher in the LAT group than in the CON group in skeletal muscle. However, DET remarkably decreased SOD2 protein expression and content in the skeletal muscle and increased malondialdehyde (MDA) level compared with LAT. Compared with LAT, DET remarkably downregulated adiponectin and upregulated tumor necrosis factor alpha (TNF-α) expression, while phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and 70-kDa ribosomal protein S6 kinase (P70S6K) protein expression decreased, and that of FoxO1 and muscle atrophy F-box (MAFbX) proteins increased in the quadriceps femoris. Adiponectin and TNF-α expression in the soleus muscle did not change between groups, whereas that of AKT, mammalian target of rapamycin (mTOR), and P70S6K was lower in the soleus in the DET group than in that in the LAT group. Compared with that in the LAT group, sestrin1 (SES1) and nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression in the DET group was lower, whereas Keap1 mRNA expression was remarkably upregulated in the quadriceps femoris. Interestingly, the protein and mRNA levels of SES1, Nrf2, and Keap1 in soleus muscle did not differ between groups. LAT remarkably upregulated ferritin heavy polypeptide 1(FTH), glutathione peroxidase 4(GPX4), and solute carrier family 7member 11 (SLC7A11) protein expression in the quadriceps femoris and soleus muscles, compared with CON. However, compared with LAT, DET downregulated FTH, GPX4, and SLC7A11 protein expression in the quadriceps femoris and soleus muscles. Long-term detraining during the aging phase reverses the improvement effect of lifelong exercise on oxidative stress, inflammation, ferroptosis, and muscle atrophy in aging skeletal muscle. The quadriceps femoris is more evident than the soleus, which may be related to the different changes in the Keap1/Nrf2 pathway in different skeletal muscles.

A Potential Target for Clinical Atherosclerosis: A Novel Insight Derived from TPM2.

Atherosclerosis (AS) is a potential inducer of numerous cardio-cerebrovascular diseases. However, little research has investigated the expression of TPM2 in human atherosclerosis samples. A total of 34 clinical samples were obtained, including 17 atherosclerosis and 17 normal artery samples, between January 2018 and April 2021. Bioinformatics analysis was applied to explore the potential role of TPM2 in atherosclerosis. Immunohistochemistry, immunofluorescence, and western blotting assays were used to detect the expression of TPM2 and α-SMA proteins. The mRNA expression levels of TPM2 and α-SMA were detected using RT-qPCR. A neural network and intima-media thickness model were constructed. A strong relationship existed between the intima-media thickness and relative protein expression of TPM2 (P<0.001, R=-0.579). The expression of TPM2 was lower in atherosclerosis than normal artery (P<0.05). Univariate logistic regression showed that TPM2 (OR=0.150, 95% CI: 0.026-0.868, P=0.034) had clear correlations with atherosclerosis. A neural network model was successfully constructed with a relativity of 0.94434. TPM2 might be an independent protective factor for arteries, and one novel biomarker of atherosclerosis.

Citrate Synthase and OGDH as Potential Biomarkers of Atherosclerosis under Chronic Stress.

BACKGROUND: Pathological changes of the adrenal gland and the possible underlying molecular mechanisms are currently unclear in the case of atherosclerosis (AS) combined with chronic stress (CS). METHODS: New Zealand white rabbits were used to construct a CS and AS animal model. Proteomics and bioinformatics were employed to identify hub proteins in the adrenal gland related to CS and AS. Hub proteins were detected using immunohistochemistry, immunofluorescence assays, and Western blotting. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze the expression of genes. In addition, a neural network model was constructed. The quantitative relationships were inferred by cubic spline interpolation. Enzymatic activity of mitochondrial citrate synthase and OGDH was detected by the enzymatic assay kit. Function of citrate synthase and OGDH with knockdown experiments in the adrenal cell lines was performed. Furthermore, target genes-TF-miRNA regulatory network was constructed. Coimmunoprecipitation (IP) assay and molecular docking study were used to detect the interaction between citrate synthase and OGDH. RESULTS: Two most significant hub proteins (citrate synthase and OGDH) that were related to CS and AS were identified in the adrenal gland using numerous bioinformatic methods. The hub proteins were mainly enriched in mitochondrial proton transport ATP synthase complex, ATPase activation, and the AMPK signaling pathway. Compared with the control group, the adrenal glands were larger and more disordered, irregular, and necrotic in the AS+CS group. The expression of citrate synthase and OGDH was higher in the AS+CS group than in the control group, both at the protein and mRNA levels (P < 0.05). There were strong correlations among the cross-sectional areas of adrenal glands, citrate synthase, and OGDH (P < 0.05) via Spearman's rho analysis, receiver operating characteristic curves, a neural network model, and cubic spline interpolation. Enzymatic activity of citrate synthase and OGDH increased under the situation of atherosclerosis and chronic stress. Through the CCK8 assay, the adrenal cell viability was downregulated significantly after the knockdown experiment of citrate synthase and OGDH. Target genes-TF-miRNA regulatory network presented the close interrelations among the predicted microRNA, citrate synthase and OGDH. After Coimmunoprecipitation (IP) assay, the result manifested that the citrate synthase and OGDH were coexpressed in the adrenal gland. The molecular docking study showed that the docking score of optimal complex conformation between citrate synthase and OGDH was -6.15 kcal/mol. CONCLUSION: AS combined with CS plays a significant role on the hypothalamic-pituitary-adrenal (HPA) axis, promotes adrenomegaly, increases the release of glucocorticoid (GC), and might enhance ATP synthesis and energy metabolism in the body through citrate synthase and OGDH gene targets, providing a potential research direction for future related explorations into this mechanism.

Ultrasound-guided, direct suprainguinal injection for fascia iliaca block for total hip arthroplasty: A retrospective study.

BACKGROUND: Peripheral regional block combined with general anesthesia might be a preferable anesthetic regimen for elderly patients undergoing total hip arthroplasty. AIM: To investigate whether ultrasound-guided, direct suprainguinal injection for fascia iliaca block accelerated recovery after general anesthesia and relieved postoperative pain after total hip arthroplasty. METHODS: Patients who underwent total hip arthroplasty under general anesthesia in 2015 or 2019 at The Second Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. The patients were grouped based on whether preoperative suprainguinal fascia iliaca block was performed or not. The time to tracheal extubation and time spent in the post-anesthesia care unit (PACU), intraoperative remifentanil dosage, fentanyl consumption in the PACU, postoperative cumulative fentanyl consumption within 48 h after operation, visual analogue scale at rest and during movement on the first and second days after surgery, and adverse reactions were compared. RESULTS: Thirty-one elderly patients who underwent total hip arthroplasty were included in the study (block group, n = 16; no-block group, n = 15). The visual analog scale scores at rest and during movement on the first and second days were significantly lower in the block group than in the no-block group (all P < 0.05). Compared with the no-block group, the intraoperative remifentanil dosage was lower, the time to tracheal extubation and the time spent in the PACU were shorter in the block group (all P < 0.01). Fentanyl consumption in the PACU and postoperative cumulative fentanyl consumption in 48 h after operation were lower in the block group (all P < 0.01). The incidence of dizziness was higher in the no-block group than in the block group (P = 0.037). CONCLUSION: Ultrasound-guided, direct suprainguinal injection for fascia iliaca block led to faster recovery after general anesthesia and early postoperative pain relief in elderly patients undergoing total hip arthroplasty.

Inhibitory effect of aloe emodin mediated photodynamic therapy on human oral mucosa carcinoma in vitro and in vivo.

We report a study on inhibition of human oral squamous cell carcinoma in vitro and in vivo, using novel photosensitizer (PS) aloe emodin (AE) mediated photodynamic therapy (PDT). Distinct morphology changes of oral mucosa carcinoma KB cells were observed under an optical microscope and cell migrations were inhibited owing to AE-PDT. The cell proliferation was blocked in G1 phase and the apoptosis increase were both caused by massive reactive oxygen species (ROS) generated from photoactivated AE. The upregulation of Caspase-3 and Bax protein levels and downregulation of Bcl-2 protein levels were observed after AE-PDT. The survival time of tumor mouse was prolonged without side effects ascribed to AE-PDT and its inhibitory effect on mice transplantation tumors was significant. It is indicated that AE mediated PDT is an innovative way to oral cancer treatment with the dominances of effectivity, minimal invasion, tissue integrity retention and none side effects on main organs.

Cisplatin combined with hyperthermia kills HepG2 cells in intraoperative blood salvage but preserves the function of erythrocytes.

The safe use of intraoperative blood salvage (IBS) in cancer surgery remains controversial. Here, we investigated the killing effect of cisplatin combined with hyperthermia on human hepatocarcinoma (HepG2) cells and erythrocytes from IBS in vitro. HepG2 cells were mixed with concentrated erythrocytes and pretreated with cisplatin (50, 100, and 200 µg/ml) alone at 37 °C for 60 min and cisplatin (25, 50, 100, and 200 µg/ml) combined with hyperthermia at 42 °C for 60 min. After pretreatment, the cell viability, colony formation and DNA metabolism in HepG2 and the Na(+)-K(+)-ATPase activity, 2,3-diphosphoglycerate (2,3-DPG) concentration, free hemoglobin (Hb) level, osmotic fragility, membrane phosphatidylserine externalization, and blood gas variables in erythrocytes were determined. Pretreatment with cisplatin (50, 100, and 200 µg/ml) combined with hyperthermia (42 °C) for 60 min significantly decreased HepG2 cell viability, and completely inhibited colony formation and DNA metabolism when the HepG2 cell concentration was 5×10(4) ml(-1) in the erythrocyte (P<0.01). Erythrocytic Na(+)-K(+)-ATPase activity, 2,3-DPG level, phosphatidylserine externalization, and extra-erythrocytic free Hb were significantly altered by hyperthermia plus high concentrations of cisplatin (100 and 200 µg/ml) (P<0.05), but not by hyperthermia plus 50 µg/ml cisplatin (P>0.05). In conclusion, pretreatment with cisplatin (50 µg/ml) combined with hyperthermia (42 °C) for 60 min effectively eliminated HepG2 cells from IBS but did not significantly affect erythrocytes in vitro.

Irradiation Can Selectively Kill Tumor Cells while Preserving Erythrocyte Viability in a Co-Culture System.

An understanding of how to safely apply intraoperative blood salvage (IBS) in cancer surgery has not yet been obtained. Here, we investigated the optimal dose of 137Cs gamma-ray irradiation for killing human hepatocarcinoma (HepG2), gastrocarcinoma (SGC7901), and colonic carcinoma (SW620) tumor cells while preserving co-cultured erythrocytes obtained from 14 healthy adult volunteers. HepG2, SGC7901, or SW620 cells were mixed into the aliquots of erythrocytes. After the mixed cells were treated with 137Cs gamma-ray irradiation (30, 50, and 100 Gy), tumor cells and erythrocytes were separated by density gradient centrifugation in Percoll with a density of 1.063 g/ml. The viability, clonogenicity, DNA synthesis, tumorigenicity, and apoptosis of the tumor cells were determined by MTT assay, plate colony formation, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, subcutaneous xenograft implantation into immunocompromised mice, and annexin V/7-AAD staining, respectively. The ATP concentration, 2,3-DPG level, free Hb concentration, osmotic fragility, membrane phosphatidylserine externalization, blood gas variables, reactive oxygen species levels, and superoxide dismutase levels in erythrocytes were analyzed. We found that 137Cs gamma-ray irradiation at 50 Gy effectively inhibited the viability, proliferation, and tumorigenicity of HepG2, SGC7901, and SW620 cells without markedly damaging the oxygen-carrying ability or membrane integrity or increasing the oxidative stress of erythrocytes in vitro. These results demonstrated that 50 Gy irradiation in a standard 137Cs blood irradiator might be a safe and effective method of inactivating HepG2, SGC7901, and SW620 cells mixed with erythrocytes, which might help to safely allow IBS in cancer surgery.

Quantitative determination of erythromycylamine in human plasma by liquid chromatography-mass spectrometry and its application in a bioequivalence study of dirithromycin.

A sensitive, rapid liquid chromatographic-electrospray ionization mass spectrometric method for determination of erythromycylamine in human plasma was developed and validated. Erythromycylamine in plasma (0.2 mL) was extracted with ethyl acetate, the organic phase was transferred to another clear 1.5 mL Eppendorf tube and evaporated to dryness under gentle nitrogen stream at 45 degrees C, and the residue was dissolved in 100 microL of mobile phase. The samples were separated using a Thermo Hypersil HyPURITY C18 reversed-phase column (150 mm x 2.1 mm I.D., 5 microm). A mobile phase containing 10 mM of ammonium acetate (pH = 6.4)-acetonitrile-methanol (50:10:40, v/v/v) was used isocratically eluting at a flow rate of 0.2 mL/min. Erythromycylamine and its internal standard (IS), midecamycin, were measured by electrospray ion source in positive selective ion monitoring mode. The method demonstrated that good linearity ranged from 4.5 to 720 ng/mL with r = 0.9997. The limit of quantification for erythromycylamine in plasma was 4.5 ng/mL with good accuracy and precision. The mean extraction recovery of the method was higher than 75.1% and 72.7% for erythromycylamine and IS, respectively. The intra-day and inter-day precision ranged from 5.2% to 6.4% and 5.6-9.3% (relative standard deviation, RSD), respectively. The established method has been successfully applied to a bioequivalence study of two dirithromycin formulations for 18 healthy volunteers.

Molecular mechanism for the potentiation of the transcriptional activity of human liver receptor homolog 1 by steroid receptor coactivator-1.

The liver receptor homolog 1 (LRH-1) belongs to the Fushi tarazu factor 1 nuclear receptor subfamily, and its biological functions are just being unveiled. The molecular mechanism for the transcriptional regulation by LRH-1 is not clear yet. In this report, we use mutagenesis and reporter gene assays to carry out a detailed analysis on the hinge region and the proximal ligand binding domain (LBD) of human (h) LRH-1 that possess important regulatory functions. Our results indicate that helix 1 of the LBD is essential for the activity of hLRH-1 and that the steroid receptor coactivator (SRC)-1 interacts directly with the LBD of hLRH-1 and significantly potentiates the transcriptional activity of hLRH-1. Cotransfection assays demonstrate that overexpressed SRC-1 potentiates hLRH-1 mediated activation of the cholesterol 7-alpha-hydroxylase promoter and increases the transcription of the endogenous cholesterol 7-alpha-hydroxylase in Huh7 cells. The interaction between SRC-1 and hLRH-1 assumes a unique pattern that involves primarily a region containing the glutamine-rich domain of SRC-1, and helix 1 and activation function-2 of hLRH-1 LBD. Mutagenesis and molecular modeling studies indicate that, similar to mouse LRH-1, the coactivator-binding cleft of hLRH-1 LBD is not optimized. An interaction between helix 1 of hLRH-1 LBD and a region containing the glutamine-rich domain of SRC-1 can provide an additional stabilizing force and enhances the recruitment of SRC-1. Similar interaction is observed between hLRH-1 and SRC-2/transcriptional intermediary factor 2 or SRC-3/acetyltransferase. Moreover, transcriptional intermediary factor 2 and acetyltransferase also potentiate the transcriptional activity of hLRH-1, suggesting a functional redundancy among SRC family members. These findings collectively demonstrate an important functional role of helix 1 in cofactor recruitment and reveal a novel molecular mechanism of transcriptional regulation and cofactor recruitment mediated by hLRH-1.