Sparassis latifolia and exercise training as complementary medicine mitigated the 5-fluorouracil potent side effects in mice with colorectal cancer: bioinformatics approaches, novel monitoring pathological metrics, screening signatures, and innovative management tactic.

BACKGROUND: Prompt identification and assessment of the disease are essential for reducing the death rate associated with colorectal cancer (COL). Identifying specific causal or sensitive components, such as coding RNA (cRNA) and non-coding RNAs (ncRNAs), may greatly aid in the early detection of colorectal cancer. METHODS: For this purpose, we gave natural chemicals obtained from Sparassis latifolia (SLPs) either alone or in conjunction with chemotherapy (5-Fluorouracil to a mouse colorectal tumor model induced by AOM-DSS. The transcription profile of non-coding RNAs (ncRNAs) and their target hub genes was evaluated using qPCR Real-Time, and ELISA techniques. RESULTS: MSX2, MMP7, ITIH4, and COL1A2 were identified as factors in inflammation and oxidative stress, leading to the development of COL. The hub genes listed, upstream regulatory factors such as lncRNA PVT1, NEAT1, KCNQ1OT1, SNHG16, and miR-132-3p have been discovered as biomarkers for prognosis and diagnosis of COL. The SLPs and exercise, effectively decreased the size and quantity of tumors. CONCLUSIONS: This effect may be attributed to the modulation of gene expression levels, including MSX2, MMP7, ITIH4, COL1A2, PVT1, NEAT1, KCNQ1OT1, SNHG16, and miR-132-3p. Ultimately, SLPs and exercise have the capacity to be regarded as complementing and enhancing chemotherapy treatments, owing to their efficacious components.

Cumulative effects of exercise training and consumption of propolis on managing diabetic dyslipidemia in adult women: a single-blind, randomized, controlled trial with pre-post-intervention assessments.

Dyslipidemia is an imbalance of various lipids, and propolis, as a natural resinous viscos mixture made by Apis mellifera L. could improve in this condition. In this single-blind, randomized trial, 60 women with type 2 diabetes and dyslipidemia were divided into four groups: (1) the patients who did not apply the combined training and 500 mg propolis capsules supplement (Control group); (2) subjects performed combined training, including aerobic and resistance training (EXR); (3) subjects received the 500 mg propolis supplement capsules (SUPP); (4) Subjects performed combined training along with receiving the 500 mg propolis supplement capsules (EXR + SUPP). We evaluated the concentration of CTRP12, SFRP5, interleukin-6 (IL6), superoxide dismutase (SOD), malondialdehyde (MDA), adiponectin, and total antioxidant capacity (TAC) before and after the intervention. MDA, TAC, IL6, CTRP12, SFRP5 IL6, adiponectin, and lipid profile levels ameliorated in the EXR + SUPP group. We found that 8 weeks of treatment by combined exercise training and propolis supplement decreased inflammation activity and increased antioxidant defense in women with diabetic dyslipidemia.Trial registration This study was registered in the Iranian Registry of Clinical Trials; IRCT code: IRCT20211229053561N1.

Swimming training and herbal nanoformulations as natural remedies to improve sensory-motor impairment in rat midbrain tumor models: system biology, behavioral test, and experimental validation.

Motor impairment worsens health-related quality of life in patients with primary and metastatic midbrain tumors. Here, 56-male-Wistar rats were divided into eight groups: Normal group, Midbrain Tomur Model group, Model + Exe group, Model + Lipo, Model + Extract, Model + Lipo-Extract, Model + Extract-Exe, Model + Lipo-Extract + Exe. According to the aim, mid-brain tumor models were conducted by injections of the C6 glioma cell line (5 × 105 cell suspension) and stereotaxic techniques in the substantia nigra area. Furthermore, consumption of nanoformulation of herbals extract (100 mg/kg/day), crude extract (100 mg/kg/day), and swimming training (30 min, 3 days/week) as interventional protocols were performed for 6 weeks. In addition, we evaluated the effect of polyherbal nanoliposomes containing four plant extracts and swimming training on the GABArα1/TRKB/DRD2/DRD1a/TH network in the substantia nigra of the midbrain tumor rat model. Data emphasized that DRD2 might be a druggable protein with the network's highest significance cut-point effect that could modulate sensory-motor impairment. Furthermore, we found Quercetin, Ginsenosides, Curcumin, and Rutin, as bioactive compounds present in Ginseng, Matthiola incana, Turmeric, and Green-Tea extracts, could bind over the DRD2 protein with approved binding affinity scores. Based on our data, swimming training, and nanoliposome-enriched combined supplements could consider effective complementary medicine for motor impairment recovery induced by the midbrain tumor in the substantia nigra area. Hence, regular swimming training and natural medicines rich in polyphenolic bioactive components and antioxidative effects could modify and improve the dopamine receptors' function. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03574-3.

Natural remedies medicine derived from flaxseed (secoisolariciresinol diglucoside, lignans, and α-linolenic acid) improve network targeting efficiency of diabetic heart conditions based on computational chemistry techniques and pharmacophore modeling.

Cytokine storms lead to cardiovascular diseases (CVDs). Natural herbal compounds are considered the primary source of active agents with the potential to prevent or treat inflammatory-related pathologies such as CVD and diabetes. Flaxseed contains phytochemicals, including secoisolariciresinol diglucoside (SDG), α-linolenic acid (ALA), and lignans, termed "SAL." Hence, we evaluated the effect of the SAL on the H9c2 cardiac cells in hyperlipidemic and hyperglycemic conditions. Here, candidate hub genes, TNF-α, IL6, SIRT1, NRF1, NPPA, and FGF7, were selected as effective genes in diabetic cardiovascular pathogenesis based on in-silico analysis and chemoinformatic. Myocardial infarction (MI) was induced using H9c2 cardiac cells in hyperlipidemic and hyperglycemic conditions. Real-time qPCR was conducted to assess the expression level of hub genes. This study indicated that SAL compounds bound to the Il-6, SIRT1, and TNF-α active sites as druggable candidate proteins based on the chemoinformatics analysis. This study displayed that the TNF-α, IL6, SIRT1, NRF1, NPPA, and FGF7 network dysfunction in MI models were ameliorated by SAL consumption. Furthermore, SAL compounds improved the function and myogenesis of H9c2 cells in hyperlipidemic and hyperglycemic conditions. Our data suggested that phytochemicals obtained from flaxseed might have proposed potential complementary treatment or preventive strategies for MI. PRACTICAL APPLICATIONS: Phytochemicals obtained from flaxseed (SAL) could reverse diabetic heart dysfunction hallmarks and provide new potential treatment approaches in cardiovascular therapy. SAL could be considered complementary and alternative medicines for treating various disorders/diseases singly or synchronizing with prescription drugs.

Regular combined training and vitamins modulated the apoptosis process in diabetic rats: Bioinformatics analysis of heart failure's differential genes expression network correlated with anti-apoptotic process.

The apoptosis process could impose significantly by hyperglycemia. According to in silico language processing and high throughput raw data analysis, we recognized hub molecular mechanisms involved in the pathogenesis of diabetic hearts and suggested a new pharmaceutical approach for declining myocardial programed cell death. Fifty male Sprague-Dawley rats were classified into five groups: healthy rats as control, diabetic rats, diabetic combined resistance/endurance training, diabetic rats which consumed supplementation vitamins E and C, and the combined supplementation and training. Here, we calculated changes in gene expression based on artificial intelligence methods and evaluated gene expression in apoptotic influencing combined training and antioxidants vitamins consumption in heart injured models by streptozotocin via Real-Time PCR. Moreover, we assessed the binding affinity of the 3D structure of small molecules on macromolecule SIRT3 to a new compound pharmaceutical suggesting the decline in cell death program. The computational intelligence surveys revealed that the apoptosis process was a remarkable pathomechanism in the abnormality function of heart tissue in diabetic conditions. Furthermore, we showed that synchronizing antioxidant vitamin consumption and regular combined training could significantly decrease irreversible myocardial cell death in diabetic myocardiopathy. Hence, levels of antiapoptotic mRNA were modified in the combined training/vitamin consumption group compared with other classifications. We found that regular combined exercise and vitamin consumption could reverse the apoptosis process to enhance the survival of cardiac muscle cells in diabetes conditions. PRACTICAL APPLICATIONS: Machine learning and system biology indicated that the apoptosis process is a vital pathomechanism of hyperglycemia-induced heart failure. Sirt3/Fas/Bcl-2/Cycs and Bax, as a critical network of apoptosis, play an essential role in heart failure induced by hyperglycemia. Moreover, Type 2 diabetes and obesity increase the risk of heart failure by increasing high blood sugar levels. We calculated the binding power of the vitamins E and C on SIRT3 protein based on the drug software. In addition, this study assessed that regular combined training and vitamin consumption had an antiapoptotic effect. Also, our data might improve the hyperglycemia state.

The functional mechanisms of synchronizing royal jelly consumption and physical activity on rat with multiple sclerosis-like behaviors hallmarks based on bioinformatics analysis, and experimental survey.

BACKGROUND: Natural nutrition and physical training have been defined as non-pharmacochemical complementary and alternative medicines to prevent and treat various pathogenesis. Royal jelly possesses various pharmacological properties and is an effective therapeutic supplement for halting neurodegeneration. Multiple sclerosis is a prevalent neurodegenerative disorder that manifests as a progressive neurological condition. Inflammation, hypoxia, and oxidative stress have been identified as significant hallmarks of multiple sclerosis pathology. RESULTS: In the present study, based on artificial intelligence and bioinformatics algorithms, we marked hub genes, molecular signaling pathways, and molecular regulators such as non-coding RNAs involved in multiple sclerosis. Also, microRNAs as regulators can affect gene expression in many processes. Numerous pathomechanisms, including immunodeficiency, hypoxia, oxidative stress, neuroinflammation, and mitochondrial dysfunction, can play a significant role in the MSc pathogenesis that results in demyelination. Furthermore, we computed the binding affinity of bioactive compounds presented in Royal Jelly on macromolecules surfaces. Also, we predicted the alignment score of bioactive compounds over the pharmacophore model of candidate protein as a novel therapeutic approach. Based on the q-RT-PCR analysis, the expression of the Dnajb1/Dnajb1/Foxp1/Tnfsf14 and Hspa4 networks as well as miR-34a-5p and miR155-3p were regulated by the interaction of exercise training and 100 mg/kg Royal Jelly (ET-100RJ). Interestingly, characteristics, motor function, a proinflammatory cytokine, and demyelination were ameliorated by ET-100RJ. DISCUSSION: Here, we indicated that interaction between exercise training and 100 mg/kg Royal jelly had a more effect on regulating the microRNA profiles and hub genes in rats with Multiple sclerosis.

Synchronized resistance training and bioactive herbal compounds of Tribulus Terrestris reverse the disruptive influence of Stanozolol.

Androgenic-Anabolic Steroids (AAS) consumption may have irreversible effects on athletes' hearts. The beneficial effects of Tribulus Terrestris (TT) have been shown to reduce cardiovascular risks through disruption in apoptosome complex construction. Therefore, this study aimed to investigate the effect of eight weeks of resistance training (RT) with TT consumption in the heart tissue of rats exposed to Stanozolol. Thirty-five male rats were divided into seven groups, Control group, Stanozolol (ST), ST + 100 mg/kg TT, ST + 50 mg/kg TT, RT + ST, RT + ST + 100 mg/kg TT, and RT + ST + 50 mg/kg TT. Differential genes expression was measured by q-RT-PCR. Artificial intelligence highlighted apoptosis pathways as a vital process in cardiovascular risks. Hence, we estimated the binding affinity of chemical and bioactive molecules on the cut point hub gene by pharmacophore modeling and molecular docking. Moreover, ST increased IL-6, Cat, Aif-1, and Caspase-9. 100 mg/kg TT has a more favorable effect than 50 mg/kg T. Also, RT with TT had interactive effects on reducing IL-6, Cat, Aif-1, and Caspase-9. RT and TT consumption seemed to synergistically reduce the apoptotic pathway markers in the heart tissue of rats exposed to the supra-physiologic dose of ST. Moreover, TT could be added to supplements and sports drink to increase an athlete's performance.

High-intensity interval training along with spirulina algae consumption and caloric restriction ameliorated the Nrf1/Tfam/Mgmt and ATP5A1 pathway in the heart tissue of obese rats.

Nrf1/Tfam/MGMT and ATP5A1 might be a pivotal network in cardiovascular disease-inducing obesity. Therefore, we evaluated eight weeks of exercise, caloric restriction, and spirulina algae consumption on the heart in obese rats. In this study, obese rats were compared with a healthy group. First, we induced obese rats with a 60%-high-fat diet. Then, after eight weeks, obese rats were randomly divided into eight groups: obese rats without treatment (HFD), obese rats treated with spirulina algae (HFD-SA), obese rats conducted exercise (HFD-EX), obese rats treated with spirulina algae and exercise (HFD-SA+EX), obese rats treated with caloric restriction (HFD-CR), obese rats treated with caloric restriction and exercise (HFD-CR+EX), obese rats treated with spirulina algae and caloric restriction (HFD-SA+CR), and obese rats treated with SA+CR+EX (HFD-SA+CR+EX). Also, the exercise protocol was performed for eight weeks, three sessions per week at an intensity of 80%-110% of maximum running speed. The spirulina algae were consumed by gavage (100 mg/kg/day), and caloric restriction used 60% of the food consumed. We found that SA+CR+EX significantly modified the Nrf1/Tfam/MGMT and ATP5A1 network in cardiovascular disease-inducing obesity rats (p < .01). Moreover, we predicted SA could be bound to Tfam and MGMT protein targets. Hence, exercise, caloric restriction, and spirulina algae had a synergistic effect on mitochondrial biogenesis in the heart tissue of obese rats (p < .01). PRACTICAL APPLICATIONS: According to artificial intelligence and medical biology servers, we discovered that mitochondrial biogenesis and oxidative stress are dominant phenomena in the cardiovascular system. Nrf1/Tfam/MGMT and ATP5A1, as pivotal regulators of oxidative stress, could play an utmost important role in the cardiovascular disease-inducing obesity molecular pathway. Furthermore, several studies have indicated that environmental factors such as the western diet and physical inactivity disrupted the mitochondrial dynamic, which led to increased reactive oxygen species (ROS). We predicted the binding power of the Spirulina's small molecules on Tfam and Mgmt proteins based on drug-discovery technology and pharmacokinetic parameters. Considering oxidative stress and mitochondrial machinery related to the action of some molecular pathways, mitochondria-related nuclear-encoded proteins, and ROS, this study evaluated the high-intensity interval training, caloric restriction, and spirulina consumption on heart mitochondrial biogenesis in obese rats. Our data might provide a novel strategy for the prevention and treatment of cardiovascular disease-inducing obesity.

An 8-Week Administration of Bifidobacterium bifidum and Lactobacillus plantarum Combined with Exercise Training Alleviates Neurotoxicity of Aß and Spatial Learning via Acetylcholine in Alzheimer Rat Model.

This study aimed to determine the effects of 8 weeks of an administration of Bifidobacterium bifidum and Lactobacillus plantarum combined with exercise training on neurotoxicity of Aß, spatial learning, acetylcholine (ACH), and vascular endothelial growth factor (VEGF) in Alzheimer rats. Twenty-five Wistar rats were randomly divided into 5 groups (n = 5 in each): (1) healthy control (control), (2) Alzheimer disease (AD), (3) AD with treadmill exercise (AD + Exe), (4) AD with probiotic (combined administration of Bifidobacterium bifidum and Lactobacillus plantarum) treatment (AD + Pro), and (5) AD with treadmill exercise and probiotic treatment (AD + Exe + Pro). AD was induced by intra-cerebroventricular injection of Aß1-42 peptide. Then, the training groups exercised on treadmill for 8 weeks, 5 days per weeks. The rats were treated daily with probiotic supplements via gavage for 8 weeks. The Morris water maze (MWM) test was administered to measure spatial learning. Then, the animals were sacrificed and Vegf and ACH were analyzed using the qPCR and immunohistochemistry (IHC) methods, respectively. Results showed that the ß-amyloid plaques were significantly increased in the brains of the AD group compared with the control group (p < 0.001). The combined use of probiotics and exercise training significantly increased the time spent in the target quadrant after removing the platform, compared with the AD group in the Morris water maze test (p < 0.001). Crystal violet analysis showed that sole (p < 0.01) and combined exercise training and probiotic supplementation (p < 0.001) significantly reduced the number of dead cells in the brains of rats compared with the AD group. AD significantly decreased Vegf mRNA and ACH in the CA1 area of the hippocampus (p < 0.001). However, mono and combined therapy (exercise and probiotics) significantly increased ACH in the rats' brain compared with the AD group. Overall, 8 weeks of an administration of Bifidobacterium bifidum and Lactobacillus plantarum combined with exercise training can improve spatial learning impairment in the AD rats. Exercise and probiotics seem to offer potential benefits to AD patients by upregulating ACH.