The introduction of Tyrosine Kinase Inhibitors (TKIs) has revolutionised cancer treatment, yet concerns regarding cardiovascular toxicity have surfaced. This piece delves into the interplay between AMP-activated protein...The introduction of Tyrosine Kinase Inhibitors (TKIs) has revolutionised cancer treatment, yet concerns regarding cardiovascular toxicity have surfaced. This piece delves into the interplay between AMP-activated protein kinase (AMPK) signalling and TKI-induced cardiovascular toxicity. The study unravels the intricate relationship between AMPK activation and TKI-induced cardiovascular toxicity, aiming to ascertain whether AMPK can play a strategic role in mitigating adverse effects. Beyond unravelling mechanistic insights, the research sets the stage for future therapeutic approaches, envisioning AMPK activation as a pivotal connection for balancing effective cancer treatment with cardiovascular well-being. As research advances, the potential of AMPK activation not only addresses challenges in TKI-induced cardiovascular toxicity but also shapes the future landscape of personalised anticancer therapies. The article explores the mechanisms of TKI-induced toxicity, AMPK's impact on cardiovascular health, and the potential therapeutic implications of AMPK activation in alleviating TKI-associated toxicities.
One of the undesirable complications of diabetes is sexual dysfunctions in males which may affect their fertility. This research aims to study the effect of C-peptide administration on the prostate of diabetic rats and f...One of the undesirable complications of diabetes is sexual dysfunctions in males which may affect their fertility. This research aims to study the effect of C-peptide administration on the prostate of diabetic rats and focusing on exploring the role of the autophagy pathway in diabetic prostate and whether it is involved in C-peptide action. Forty adult male Wistar albino rats were separated into control group, diabetic group, diabetic + C-peptide and diabetic + C-peptide + 3-Methyladenine (autophagy inhibitor). Serum metabolic parameters and prostatic specific antigen (PSA) were measured. Markers of oxidative stress, inflammation, fibrosis, cell proliferation and cell autophagy were evaluated in prostate tissues using biochemical, western blotting and immunohistochemical techniques. C-peptide administration ameliorated the effects of diabetes on the prostate through its hypoglycaemic, antioxidant, anti-inflammatory, and antiproliferative effects which were reversed with autophagy inhibition. Thus, we concluded that C-peptide prevented the effects of diabetes on the prostate through stimulation of the autophagy pathway.
Hassan FE, Aboulhoda BE, Mehesen MN
… +9 more, El Din PM, Abdallah HA, Bendas ER, Ahmed Rashed L, Mostafa A, Amer MF, Abdel-Rahman M, Alghamdi MA, Shams Eldeen AM
CONTEXT: Insulin resistance and a disturbed lipid profile are common associations with type 2 diabetes mellitus (T2DM) and different skin diseases, particularly psoriasis (PsO). OBJECTIVES: We investigated potential ther...CONTEXT: Insulin resistance and a disturbed lipid profile are common associations with type 2 diabetes mellitus (T2DM) and different skin diseases, particularly psoriasis (PsO). OBJECTIVES: We investigated potential therapeutic mechanisms of metformin in a murine animal model of psoriasiform lesions in T2DM. MATERIALS AND METHODS: Forty-two rats were randomly divided into control, PsO, and type II DM (T2DM) groups. After confirmation of DM, the type II diabetic rats were allocated into T2DM+ PsO, T2DM+ PsO+ systemic metformin (S. met), T2DM+ PsO+ topical metformin (T. met)), and T2DM+ PsO + combined metformin (C. met). PsO was induced by topical imiquimod. RESULTS: Systemic administration of the cornerstone antidiabetic drug, metformin, was able to improve insulin resistance and lipid profile. At molecular levels, both topical and systemic metformin significantly increased AMP-activated protein kinase (AMPK), and lowered keratinocyte growth factor (KGF) / "Signal transducer and activator of transcription" (STAT)3 protein levels, and the IL-17RA and IL-17RC gene expression. CONCLUSION: Although its glucose-controlling effect was not optimum, T.met gel served anti-psoriatic and anti-inflammatory effects.
infection has been associated with the development of insulin resistance (IR). This study aimed to examine the effect of -derived extracellular vesicles (EVs) on IR induction. EVs were derived from two strains, and char...infection has been associated with the development of insulin resistance (IR). This study aimed to examine the effect of -derived extracellular vesicles (EVs) on IR induction. EVs were derived from two strains, and characterised by transmission electron microscopy and dynamic light scattering. Different concentrations of insulin were added to HepG2 cells to induce IR model. HepG2 cells were exposed to various concentrations of -derived EVs to assess IR development. The gene expression of , , , , , and miR-140 was examined using RT-qPCR. Glucose uptake analysis revealed insulin at 5 × 10 mol/l and EVs at 50 µg/ml induced IR model in HepG2 cells. -derived EVs downregulated the expression level of , , and , and upregulated , , , and miR-140 expression in HepG2 cells. In conclusion, our findings propose a novel mechanism by which derived EVs could potentially induce IR.
CONTEXT: Energy homeostasis is a primary factor for the survival of mammals. Many tissues and organs, among which is the liver, keep this homeostasis in varied circumstances, including caloric restriction (CR) and physic...CONTEXT: Energy homeostasis is a primary factor for the survival of mammals. Many tissues and organs, among which is the liver, keep this homeostasis in varied circumstances, including caloric restriction (CR) and physical activity. OBJECTIVE: This study investigated glucose metabolism using the following groups of eight-week-old male Swiss mice: CS, sedentary and fed freely; RS, sedentary and RT, trained, both under 30% CR ( = 20-23 per group). RESULTS: Organs and fat depots of groups RS and RT were similar to CS, although body weight was lower. CR did not impair training performance nor affected systemic or hepatic glucose metabolism. Training combined with CR (group RT) improved glucose tolerance and did not affect liver gluconeogenesis. CONCLUSIONS: The mice tolerated the prolonged moderate CR without impairment of their well-being, glucose homeostasis, and resistance training performance. But the higher liver gluconeogenic efficiency previously demonstrated using this training protocol in mice was not evidenced under CR.
BACKGROUND: Diabetes patients' quality of life can be severely impacted by diabetic muscle atrophy. AIM: This study aimed to explore the impact of high-intensity exercise (HIE) alongside insulin treatment on muscle atrop...BACKGROUND: Diabetes patients' quality of life can be severely impacted by diabetic muscle atrophy. AIM: This study aimed to explore the impact of high-intensity exercise (HIE) alongside insulin treatment on muscle atrophy in a rat model of type 1 diabetes mellitus (T1DM). METHODOLOGY: Fifty rats were allocated into five groups; Group 1, control sedentary (CS), T1DM was elicited in the rest of the groups by giving them Streptozotocin (STZ) (60 mg/kg), where group 2 (DS) remained sedentary, while groups 3,4,5 were treated with insulin after induction of diabetes. Group 4 (DI+MIE) and 5 (DI+ HIE) underwent moderate and high-intensity exercise, respectively. RESULTS: HIE for 14 days combined with insulin treatment significantly restored muscle strength and mass with a significant modification in the mitophagy-related proteins and fibroblast growth factor 21 (FGF 21) compared to other treated groups. CONCLUSION: This study concluded that there is a therapeutic role for HIE with insulin against T1DM-induced muscle atrophy.
Obese adipose tissue produces various pro-inflammatory cytokines that are major contributors to adipose tissue inflammation. The present study aimed to determine the effects of HM-chromanone (HMC) against obesity and ad...Obese adipose tissue produces various pro-inflammatory cytokines that are major contributors to adipose tissue inflammation. The present study aimed to determine the effects of HM-chromanone (HMC) against obesity and adipose tissue inflammation in high-fat diet-fed mice. Twenty-four C57BL/6J male mice were divided into three groups: ND (normal diet), HFD (high-fat diet), and HFD + HMC. The ND group was fed a normal diet, whereas the HFD and HFD + HMC groups were fed a high-fat diet. After 10 weeks of feeding, the animals were orally administered the treatments daily for 9 weeks. The ND and HFD group received distilled water as treatment. The HFD+HMC group was treated with HM-chromaone (50 mg/kg). HM-chromanone administration decreased body weight, fat mass, and adipocyte diameter. HM-chromanone also improved plasma lipid profiles, decreased leptin levels, and increased adiponectin levels. The inhibiting effect of HM-chromanone on SREBP-1c, PPARγ, C/EBPα, and FAS decreased adipogenesis, thereby alleviating lipid accumulation. Furthermore, HM-chromanone administration exhibited a reduction in macrophage infiltration and the expression of pro-inflammatory cytokines. HM-chromanone suppressed the phosphorylation of IκBα and NF-κB, leading to the inhibition of iNOS and COX2 expressions, resulting in decreased inflammation in adipose tissue. These results highlight the anti-obesity and anti-inflammatory properties of HM-chromanone, achieved through the downregulation of the SREBP-1c and NF-κB pathway in high-fat diet-fed mice.
Diabetic kidney disease (DKD) is one of the common microvascular complications of diabetes, and there are still lack of effective treatments. Huaiqihuang (HQH) is a kind of traditional Chinese medicine mixed preparation,...Diabetic kidney disease (DKD) is one of the common microvascular complications of diabetes, and there are still lack of effective treatments. Huaiqihuang (HQH) is a kind of traditional Chinese medicine mixed preparation, which is mainly made of Trametes robiniophila Murr, Fructus Lycii, and Polygonatum sibiricumhas. It has been shown to be effective in the treatment of DKD, but the specific mechanism has not been fully elucidated. Our results showed that HQH increased the protein expressions of synaptopodin, podocin, WT-1, and Bcl-2, decreased the protein expressions of Bax and cleaved-casepase-3, and activated the NF-ĸB and PI3K/AKT/mTOR pathway in MPC5 cells exposed to high-glucose (HG). Real-time PCR results showed that HQH reduced the mRNA expression of TNF-α, IL-1β, MCP-1, and IL-6. In conclusion, our results showed that HQH may attenuate podocyte injury by inhibiting MPC5 cell apoptosis induced by HG and NF-κB-mediated inflammation response through activation of the PI3K/AKT/mTOR pathway.
Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage degeneration and damage. Increasing circular RNAs (circRNAs) have been identified to participate in the pathogenesis of OA. Hsa_circ_012...Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage degeneration and damage. Increasing circular RNAs (circRNAs) have been identified to participate in the pathogenesis of OA. Hsa_circ_0128006 (also known as circSEC24) was reported as an upregulated circRNA in OA tissues, but its biological role and underlying mechanism in OA are still to be discussed. circSEC24A and NAMPT expression levels were upregulated, and miR-515-5p was reduced in OA cartilage tissues and IL-1β-treated CHON-001 cells. The absence of circSEC24A overturned IL-1β-induced suppression of cell viability and promotion of oxidative stress, apoptosis, extracellular matrix (ECM) degradation, and inflammation in CHON-001 cells. Mechanistically, circSEC24A acted as a molecular sponge for miR-515-5p to affect NAMPT expression. CircSEC24A knockdown could attenuate IL-1β-triggered CHON-001 cell injury partly via the miR-515-5p/NAMPT axis, providing new insight into the underlying application of circSEC24A in OA treatment.
In this study, the anti-inflammatory, antioxidative, and protective effects of ghrelin were investigated in a fat-fed streptozotocin (STZ) rat model and compared with metformin, diabetes and the healthy control groups. H...In this study, the anti-inflammatory, antioxidative, and protective effects of ghrelin were investigated in a fat-fed streptozotocin (STZ) rat model and compared with metformin, diabetes and the healthy control groups. Histopathological evaluations were performed on H&E-stained pancreas and brain sections. Biochemical parameters were investigated by enzyme-linked immunosorbent assay. Blood glucose levels were significantly decreased with ghrelin or metformin treatments than the diabetes group. STZ administration increased brain, renal and pancreatic IL-1β, TNF-α and MDA while decreasing GPX, CAT, SOD, and NGF levels. Ghrelin increased renal GPX, CAT, NGF pancreatic GPX, SOD, CAT, NGF and brain SOD, NGF while it decreased renal, pancreatic and brain IL-1β, TNF-α and MDA levels. Ghrelin reduced neuronal loss and degeneration in the cerebral cortex and hippocampus and greatly ameliorated diabetes-related damage in pancreas. In conclusion, the data suggested that ghrelin is an effective candidate as a protectant for reducing the adverse effects of diabetes.
Ningsih S, Agustini K, Kusumaningrum S
… +11 more, Firdausi N, Eru Wibowo A, Efendi J, Ngatinem N, Subiantoro AH, Suparjo S, Catherine C, Auni Rabbina N, Bahtiar A, Damayanti R, Lee K
This study aimed to evaluate the anti-inflammatory activity of the combination of Vahl. and Roxb. (AC) extract in monosodium iodoacetate (MIA)-induced osteoarthritis (OA) rat model. AC was administered orally to OA rat...This study aimed to evaluate the anti-inflammatory activity of the combination of Vahl. and Roxb. (AC) extract in monosodium iodoacetate (MIA)-induced osteoarthritis (OA) rat model. AC was administered orally to OA rats (240, 480, and 960 mg/kg bw) for three weeks. The control and model groups comprised OA rats treated with diclofenac sodium and carrier, respectively. AC-treated rats exhibited a significant reduction in oedema volume compared to those of the model group (p < 0.05). Notably, AC, at 960 mg/kg bw, significantly decreased inflammatory cytokines TNF-α and IL-1β, along with matrix metalloproteinase-9 (MMP-9) levels compared to those of the model group (p < 0.05). AC's attenuation of OA progression was also observed through haematoxylin and eosin (H&E) and Safranin O-fast green analysis. A phytochemical study showed AC contained phenolic, flavonoid, curcumin, demethoxycurcumin, and bisdemethoxycurcumin compounds. This study concludes that AC alleviated OA progression through anti-inflammatory effects and depressed MMP-9 levels.
INTRODUCTION: Postmenopausal diabetes is a condition that affects millions of women and their quality of life. Also, kidney and small intestine tissues are damaged due to diabetes. The present study aimed to examine the...INTRODUCTION: Postmenopausal diabetes is a condition that affects millions of women and their quality of life. Also, kidney and small intestine tissues are damaged due to diabetes. The present study aimed to examine the protective effects of an extract prepared from leaves on kidney and small intestine tissues against experimentally created postmenopausal diabetes. METHODS: For this purpose, experimental rats were randomly divided into six groups (Control; ovariectomy:OVX, diabetic:D, ovariectomy + diabetic:OVX + D, ovariectomy + diabetic + oestrogen:OVX + D+E2, ovariectomy + diabetic + MC: OVX + D+MC) and kidney and small intestine tissues were taken after the experimental procedure. RESULTS: Evaluations of biochemical parameters (glutathione and glutathione-related enzymes, antioxidant enzymes, etc.) showed that MC had a protective effect on kidney and small intestine tissues in diabetes and ovariectomy groups. CONCLUSION: It can be suggested that MC extract has a protective effect on small intestine and kidney tissues in postmenopausal diabetes and may be a good herbal source for this purpose.
AIM: This study examined the effects of hyperthermic therapy (HT) on mice fed normal chow or a high-fat diet (HFD) for 18 or 22 weeks, undergoing four or eight weekly HT sessions. METHODS: Mice were housed within their t...AIM: This study examined the effects of hyperthermic therapy (HT) on mice fed normal chow or a high-fat diet (HFD) for 18 or 22 weeks, undergoing four or eight weekly HT sessions. METHODS: Mice were housed within their thermoneutral zone (TNZ) to simulate a physiological response. HFD-induced obesity-related changes, including weight gain, visceral fat accumulation, muscle loss (indicative of obesity sarcopenia), glucose intolerance, and hepatic triglyceride buildup. MAIN RESULTS: HT upregulated HSP70 expression in muscles, mitigated weight gain, normalised QUICK index, and reduced plasma HSP70 concentrations. It also lowered the H-index of HSP70 balance, indicating improved immunoinflammatory status, and decreased activated caspase-1 and proliferative senescence in adipose tissue, both linked to insulin resistance. CONCLUSION: The findings suggest that even animals on a "control" diet but with insufficient physical activity and within their TNZ may experience impaired glycaemic homeostasis.
Neuropathic pain, a nerve damage consequence, presents symptoms such as dysesthesia, hyperalgesia, and allodynia. This study aimed to evaluate the alleviating potential of artichoke leaf extract in neuropathic pain induc...Neuropathic pain, a nerve damage consequence, presents symptoms such as dysesthesia, hyperalgesia, and allodynia. This study aimed to evaluate the alleviating potential of artichoke leaf extract in neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in male rats. The hydroethanolic extract of artichoke leaf was administered via gavage at doses of 200, 400, and 800 mg/kg for 21 days. Behavioural tests were conducted on days 1, 4, 7, 14, and 21 post-surgeries. Only the dose of 800 mg/kg significantly reduced thermal hyperalgesia and allodynia from day 14 and mechanical allodynia from day 7, and the other doses did not affect behaviours. Biochemical analysis showed that artichoke extract decreased lipid peroxidation and restored antioxidant enzyme activities (SOD and GPx) in the sciatic nerve tissue. In conclusion, artichoke leaf extract administration diminishes neuropathic pain-related behaviours by enhancing antioxidant capacity and reducing oxidative stress in the rats' sciatic nerve.
AIM: This study assessed the efficacy of costunolide (COST) against oxidative tissue damage in the ovarian torsion/detorsion (TD) model. METHODOLOGY: Animals were randomly assigned to sham, ovarian TD, COST 5 mg/kg + ova...AIM: This study assessed the efficacy of costunolide (COST) against oxidative tissue damage in the ovarian torsion/detorsion (TD) model. METHODOLOGY: Animals were randomly assigned to sham, ovarian TD, COST 5 mg/kg + ovarian TD, and COST 10 mg/kg + ovarian TD groups. COST's effectiveness was determined by assessing oxidative stress markers, interleukin levels, and histopathological examinations. RESULTS: Oxidative stress markers were elevated in the ovarian TD group compared to the sham group. COST treatment represented a decline compared to the TD group. Besides, the antioxidant activity was significantly higher in the ovarian TD group than in the sham group. COST treatment improved the antioxidant parameters compared to the TD group. Inflammatory parameters, such as tumour necrosis factor- alpha (TNF-α) and interleukin 1-beta (IL-1β) were higher in the ovarian TD group than the sham group. CONCLUSION: COST treatment suppressed the proinflammatory cytokine expression compared to the TD group. Histopathological data supported these findings.
BACKGROUND: One of the most popular chemotherapy medications is doxorubicin (DOX), however it can have non-negligible damage. When the underlying mechanisms of damage are investigated, the most prominent pathways are oxi...BACKGROUND: One of the most popular chemotherapy medications is doxorubicin (DOX), however it can have non-negligible damage. When the underlying mechanisms of damage are investigated, the most prominent pathways are oxidative stress, inflammation and apoptosis. AIM: We investigated the NF-κB/MAPK inflammatory pathway and cellular apoptosis to determine the efficacy of trigonelline alkaloid (TRIG) in preventing DOX-induced lung injury. METHODOLOGY: The study consisted of C, TRIG, DOX and TRIG+DOX groups. TRIG and TRIG+DOX groups received 50 mg/kg TRIG for 7 days. On day 8, DOX and TRIG+DOX groups received a single dose of 15 mg/kg DOX. RESULTS: Our results showed that apoptosis markers and inflammation were higher in the DOX group. In contrast, TRIG pretreatment partially suppressed apoptosis and decreased inflammation by blocking the activation of the MAPK/NF-κB pathway, lowering IL-6 levels, and protecting the lung from apoptotic cell death. CONCLUSION: Assessing TRIG's effectiveness in lung tissue injury, this study may be a crucial first step.
CONTEXT: Ferroptosis is a novel form of cell death characterised by iron overload and lipid peroxidation. It is closely associated with many diseases, including cardiovascular diseases, tumours, and neurological diseases...CONTEXT: Ferroptosis is a novel form of cell death characterised by iron overload and lipid peroxidation. It is closely associated with many diseases, including cardiovascular diseases, tumours, and neurological diseases. The use of natural chemicals to modulate ferroptosis is of great concern because of the critical role ferroptosis plays in disease. The main active ingredient in green tea is epigallocatechin gallate (EGCG), which is the most abundant catechin in green tea. EGCG shows a wide range of biological and therapeutic effects in various diseases, including anti-inflammatory, antioxidant, anticancer, and cardioprotective. OBJECTIVE: The purpose of this article is to summarise the existing information on the relationship between EGCG and ferroptosis. METHODS: Articles related to EGCG and ferroptosis were searched in PubMed and Web of Science databases, and the literature was analysed. RESULTS AND CONCLUSION: EGCG could improve ferroptosis-related diseases and affect the development of ferroptosis by regulating the nuclear factor erythroid 2-related factor 2, autophagy, microRNA, signal transducer and activator of transcription 1, and protein kinase D1 signalling pathways.
The aim of this study was to investigate the protective effects of Mangiferin (MG) on glucolipotoxicity-induced pancreatic beta-cell injury. In vivo administration of MG significantly reduced the level of blood glucose i...The aim of this study was to investigate the protective effects of Mangiferin (MG) on glucolipotoxicity-induced pancreatic beta-cell injury. In vivo administration of MG significantly reduced the level of blood glucose in high-fat diet (HFD)-fed mice. MG treatment inhibited beta-cell apoptosis in HFD-treated mice. MG protected INS-1 cells against apoptosis and impairment of insulin secretion following High glucose/Palmitic acid (HG/PA) treatment. MG treatment enhanced autophagy flux which was blocked by HG/PA treatment. Inhibition of autophagosome formation by 3-Methyladenine or blockade of autolysosome by Chloroquine reversed the protective effects of MG on INS-1 cells. MG treatment increased AMPK phosphorylation and reduced mTOR activation in INS-1 cells. Administration of the AMPK blocker abrogated MG-induced autophagy, and similar results were observed in INS-1 cells after cotreatment with MG and mTOR activator. In conclusion, MG ameliorated pancreatic beta-cell injury induced by glucolipotoxicity through modulation of autophagy via the AMPK-mTOR pathway.
This study aimed to investigate the effects and molecular mechanism of PF on high glucose (HG)-induced podocyte injury. Results found that PF increased proliferation activity, decreased apoptosis, LDH, and caspase-3 leve...This study aimed to investigate the effects and molecular mechanism of PF on high glucose (HG)-induced podocyte injury. Results found that PF increased proliferation activity, decreased apoptosis, LDH, and caspase-3 levels, and increased nephrin and podocin expression in HG-induced cells. Similarly, PF improved HG-induced mitochondrial damage, decreased Ca and ROS content, alleviated oxidative stress, inhibited mPTP opening, increased mitochondrial membrane potential, and decreased the expressions of Drp1, Bak, Bax, and Cytc in cytoplasm, increased the expressions of SIRT1, PGC-1α, HSP70, HK2, and Cytc in mitochondria of podocytes. The use of mPTP agonist/blocker and SIRT1 inhibitor confirmed that PF alleviates HG-induced podocyte injury by regulating mitochondrial mPTP opening through SIRT1/PGC-1α. In addition, PF affected HK2-VDAC1 protein binding to regulate mPTP opening via the SIRT1/PGC-1α pathway. In conclusion, PF-regulated HK2-VDAC1 protein binding affected mitochondrial mPTP opening and improved HG-induced podocyte injury through the SIRT1/PGC-1α pathway.