Iranian Journal of Basic Medical Sciences最新文献

Objectives: In this study, the SP-38 (Diterpene Lactone derivative) was designed, synthesized from clerodane diterpene (lactone) isolated from Polyanthia longifolia var. pendula, and tested for anti-arthritic activity using the FCA-induced arthritic rat model.

Materials and methods: This study examined the in vivo effects of SP-38 using three different doses (20, 10, and 5 mg/kg) by oral administration for 21 days from day 8 after 0.1 ml FCA sub-planter injection until day 28. Arthritis index, paw swelling, ankle diameter, body weight as well as biochemical, hematological, histopathological, and radiological parameters were examined.

Results: Administered SP-38 reduced arthritis index, paw volume, and joint swelling compared to the arthritic control group. Accordingly, rats treated with SP-38 showed a remarkable increase in body weight and improved biochemical, hematological, histopathological, and radiological parameters. Furthermore, it reduced the increased production of CRP and RF while simultaneously decreasing ESR in all SP-38-treated rats. However, SP-38 showed promising liver protection by reducing elevated serum levels of liver and kidney function markers SGOT, SGPT, and ALP. Furthermore, splenic index, TNF-α, and IL-6 levels were significantly reduced compared to arthritic control rats at certain doses.

Conclusion: The result of the present study concludes that SP-38 has significant anti-arthritic potential in FCA-induced arthritis in Wistar rats. SP-38 therefore showed promising anti-arthritic activity, as evidenced by attenuation of inflammation, inflammatory markers, and pro-inflammatory cytokine levels.

Objectives: Mesenchymal stem cell (MSC) transplantation represents a promising approach for treating Alzheimer's disease (AD). These stem cells, however, have a short lifespan following transplantation into recipient animals. Selenium nanoparticles, due to their size, aid in drug delivery for brain disorders. This study investigated the therapeutic effect of MSCs and polyvinyl alcohol (PVA)-coated selenium nanoparticles (SeNPs) in a rat model of AD.

Materials and methods: An Alzheimer-like phenotype was induced through intracerebroventricular (ICV) administration of streptozotocin (STZ). Rats were assigned to five groups: control, Alz (STZ; 3 mg/kg, 10 μl, ICV), Alz+stem cell (ICV transplantation), Alz+SeNP (0.4 mg/kg, orally), and Alz+stem cell+SeNPs. The ICV administration of STZ mimicked some aspects of AD in the Alz groups. SeNPs were administrated for 30 days following STZ administration. The novel object recognition (NOR) and passive avoidance learning (PAL) tests were used to evaluate cognition and memory. Oxidative stress biomarkers and brain-derived neurotrophic factor (BDNF) were assessed by biochemical analysis, ELISA kits, and Congo red staining, respectively.

Results: The combined therapy of PVA-coated SeNPs and MSC transplantation was more effective in enhancing memory reacquisition compared to either SeNPs or MSCs alone. The use of stem cells in conjunction with PVA-coated SeNPs significantly boosted anti-oxidant capacity.

Conclusion: The results suggest that the joint treatment with PVA-coated SeNPs and MSCs offers considerable neuroprotection against AD in animal models.

Metabolic syndrome (MetS) is a widespread global epidemic that affects individuals across all age groups and presents a significant public health challenge. Comprising various cardio-metabolic risk factors, MetS contributes to morbidity and, when inadequately addressed, can lead to mortality. Current therapeutic approaches involve lifestyle changes and the prolonged use of pharmacological agents targeting the individual components of MetS, posing challenges related to cost, compliance with medications, and cumulative side effects. To overcome the challenges associated with these conventional treatments, herbal medicines and phytochemicals have been explored and proven to be holistic complements/alternatives in the management of MetS. Thymoquinone (TQ), a prominent bicyclic aromatic compound derived from Nigella sativa emerges as a promising candidate that has demonstrated beneficial effects in the treatment of the different components of MetS, with a good safety profile. For methodology, literature searches were conducted using PubMed and Google Scholar for relevant studies until December 2023. Using Boolean Operators, TQ and the individual components of MetS were queried against the databases. The retrieved articles were screened for eligibility. As a result, we provide a comprehensive overview of the anti-obesity, anti-dyslipidaemic, anti-hypertensive, and anti-diabetic effects of TQ including some underlying mechanisms of action such as modulating the expression of several metabolic target genes to promote metabolic health. The review advocates for a paradigm shift in MetS management, it contributes valuable insights into the multifaceted aspects of the application of TQ, fostering an understanding of its role in mitigating the global burden of MetS.

Objectives: Chronic pain is considered as pain lasting for more than three months and has emerged as a global health problem affecting individuals and society. Chronic extensive pain is the main syndrome upsetting individuals with fibromyalgia (FM), accompanied by anxiety, obesity, sleep disturbances, and depression, Transient receptor potential vanilloid 1 (TRPV1) has been reported to transduce inflammatory and pain signals to the brain.

Materials and methods: Acupoint catgut embedding (ACE) is a novel acupuncture technique that provides continuous effects and convenience. ACE was performed at the bilateral ST36 acupoint.

Results: We demonstrated similar pain levels among all groups at baseline. After cold stress, chronic mechanical or thermal nociception was induced (D14: mechanical: 1.85 ± 0.13 g; thermal: 4.85 ± 0.26 s) and reversed in ACE-treated mice (D14: mechanical: 3.99 ± 0.16 g; thermal: 7.42 ± 0.45 s) as well as Trpv1^-/- group (Day 14, mechanical: 4.25 ± 0.2 g; thermal: 7.91 ± 0.21 s) mice. Inflammatory mediators were augmented in FM individuals and were abridged after ACE management and TRPV1 gene loss. TRPV1 and its linked mediators were increased in the thalamus (THA), somatosensory cortex (SSC), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC) in FM mice. The up-regulation of these mediators was diminished in ACE and Trpv1^-/- groups.

Conclusion: We suggest that chronic pain can be modulated by ACE or Trpv1^-/-. ACE-induced analgesia via TRPV1 signaling pathways may be beneficial targets for FM treatment.

Objectives: To investigate the effects and mechanisms of ivabradine (IVA) on isoprenaline-induced cardiac injury.

Materials and methods: Forty male C57BL/6 mice were randomly divided into control group, model group, high-dose IVA group, and low-dose IVA group. The control group was given saline, other groups were given subcutaneous injections of isoproterenol (ISO) 5 mg/kg/d to make the myocardial remodeling model. A corresponding dose of IVA (high dose 50 mg/kg/d, low dose 10 mg/kg/d) was given by gavage (30 days). A transthoracic echocardiogram was obtained to detect the structure and function of the heart. An electron microscope was used to explore the cardiomyocytes' apoptosis and autophagy. HE staining and Masson's trichrome staining were performed to explore myocardial hypertrophy and fibrosis. Western blot was used to detect Bax, Bcl-2, cleaved caspase-3, Becline-1, LC3, phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK), phosphorylated extracellular regulated protein kinases1/2 (p-ERK1/2), phosphorylated c-Jun N-terminal kinase (p-JNK), and α-smooth muscle actin (α-SMA) in the myocardium.

Results: Heart rate in the IVA groups was reduced, and the trend of heart rate reduction was more obvious in the high-dose group. Echocardiography showed that IVA improved the cardiac structure and function compared to the model group. IVA attenuated cardiac fibrosis, decreased cardiomyocyte apoptosis, and increased autophagy. The phosphorylated MAPK in the ISO-induced groups was increased. IVA treatment decreased the p-p38MAPK level. There were no differences in p-ERK and p-JNK levels.

Conclusion: The beneficial effects of IVA on myocardial injury are related to blocking the p38MAPK signal pathway, decreasing cardiomyocyte apoptosis, and increasing cardiomyocyte autophagy.

Objectives: Knowing the detrimental role of oxidative stress in wound healing and the anti-oxidant properties of Dexpanthenol (Dex), we aimed to produce Dex-loaded electrospun core/shell nanofibers for wound healing study. The novelty was measuring oxidative stress in wounds to know how oxidative stress was affected by Dex-loaded fibers.

Materials and methods: TPVA solution containing Dex 6% (w/v) (core) and PVA/chitosan solution (shell) were coaxially electrospun with variable injection rates of the shell solution. Fibers were then tested for physicochemical properties, drug release profile, and effects on wound healing. Levels of tissue lipid peroxidation and superoxide dismutase activity were measured.

Results: Fibers produced at shell injection rate of 0.3 ml/hr (F3 fibers) showed core/shell structure with an average diameter of 252 nm, high hydrophilicity (swelling: 157% at equilibrium), and low weight loss (13.6%). Dex release from F3 fibers seemed to be ruled by the Fickian mechanism based on the Korsmeyer-Peppas model (R² = 0.94, n = 0.37). Dex-loaded F3 fibers promoted fibroblast viability (128.4%) significantly on day 5 and also accelerated wound healing compared to the neat F3 fibers at macroscopic and microscopic levels on day 14 post-wounding. The important finding was a significant decrease in malondialdehyde (0.39 nmol/ mg protein) level and an increase in superoxide dismutase (5.29 unit/mg protein) activity in Dex-loaded F3 fiber-treated wound tissues.

Conclusion: Dex-loaded core/shell fibers provided nano-scale scaffolds with sustained release profile that significantly lowered tissue oxidative stress. This finding pointed to the importance of lowering oxidative stress to achieve proper wound healing.

Objectives: Bone tissue engineering is considered a new method in the treatment of bone defects and can be an effective alternative to surgery and bone grafting. The use of adipose tissue mesenchymal stem cells (ADMSCs) on synthetic polymer scaffolds is one of the new approaches in bone tissue engineering. In this study, we aimed to investigate the effect of laminin coating on biocompatibility and osteogenic differentiation of ADMSCs seeded on polycaprolactone (PCL) scaffolds.

Materials and methods: The morphology of the electrospun scaffold was evaluated using a scanning electron microscope (SEM). Cell proliferation and cytotoxicity were determined by MTT assay. The adipogenic and osteogenic differentiation potential of the cells was evaluated. The osteogenic differentiation of ADMSCs cultured on the PCL scaffold coated with laminin was assessed by evaluating the level of alkaline phosphatase (ALP) activity, intracellular calcium content, and expression of bone-specific genes.

Results: The results showed that the ADMSCs cultured on PCL/laminin showed enhanced osteogenic differentiation compared to those cultured on non-coated PCL or control medium (P<0.05).

Conclusion: It seems that laminin enhances the physicochemical properties and biocompatibility of PCL nanofiber scaffolds; and by modifying the surface of the scaffold, improves the differentiation of ADMSCs into osteogenic cells.

Objectives: Bevacizumab is a commonly used anticancer drug in clinical practice, but it often leads to adverse reactions such as vascular endothelial damage, hypertension, arterial and venous thrombosis, and bleeding. This study investigated the protective effects of metformin against bevacizumab-induced vascular injury in a mouse model and examined the possible involvement of GDF15/PI3K/AKT/FOXO/PPARγ signaling in the effects.

Materials and methods: C57 male mice were purchased. To investigate metformin, the mice were assigned to the saline, bevacizumab (15 mg every 3 days), metformin (1200 mg/day), and bevacizumab+metformin groups. To investigate GDF15, the mice were assigned to the siNC+bevacizumab, siNC+bevacizumab+metformin, siGDF15+bevacizumab, and siGDF15+bevacizumab+metformin groups. Histological staining was used to evaluate vascular injury. Flow cytometry was used to evaluate apoptosis. ELISA was used to measure plasma endothelial injury markers and proinflammatory cytokines. qRT-PCR and western blot were used to determine the expression of GDF15 and PI3K/AKT/FOXO/PPARγ in aortic tissues.

Results: Metformin alleviated bevacizumab-induced abdominal aortic injury, endothelial cell apoptosis, and systemic inflammation in mice (all P<0.05). Metformin up-regulated GDF15 expression and PI3K/AKT/FOXO/PPARγ signaling in the abdominal aorta of mice treated with bevacizumab (all P<0.05). siGDF15 abolished the vascular protective and anti-inflammatory effects of metformin (all P<0.05). siGDF15 suppressed PI3K/AKT/FOXO/PPARγ signaling in the abdominal aorta of mice treated with bevacizumab (all P<0.05).

Conclusion: Metformin attenuates bevacizumab-induced vascular endothelial injury, apoptosis, and systemic inflammation by activating GDF15/PI3K/AKT/FOXO/PPARγ signaling.

Crocus sativus L. was used for the treatment of a wide range of disorders in traditional medicine. Due to the extensive protective and treatment properties of C. sativus and its constituents in various diseases, the purpose of this review is to collect a summary of its effects, on experimental studies, both in vitro and in vivo. Databases such as PubMed, Science Direct, and Scopus were explored until January 2023 by employing suitable keywords. Several investigations have indicated that the therapeutic properties of C. sativus may be due to its anti-oxidant and anti-inflammatory effects on the nervous, cardiovascular, immune, and respiratory systems. Further research has shown that its petals also have anticonvulsant properties. Pharmacological studies have shown that crocetin and safranal have anti-oxidant properties and through inhibiting the release of free radicals lead to the prevention of disorders such as tumor cell proliferation, atherosclerosis, hepatotoxicity, bladder toxicity, and ethanol induced hippocampal disorders. Numerous studies have been performed on the effect of C. sativus and its constituents in laboratory animal models under in vitro and in vivo conditions on various disorders. This is necessary but not enough and more clinical trials are needed to investigate unknown aspects of the therapeutic properties of C. sativus and its main constituents in different disorders.

Objectives: During aging, cerebral structures undergo changes due to oxidative stress. The consumption of some plants seems to improve neurological health. For example, rosemary extract (RE) which is widely used as a flavoring food has anti-inflammatory and anti-oxidant activities. Therefore, we aimed to study the effect of RE on the changes related to the aging process in the prefrontal cortex (PFC).

Materials and methods: Twenty-four male Wistar rats including young and old were purchased. Each group was divided into two subgroups: vehicle and rosemary (old vehicle (OV), old rosemary (OR), young vehicle (YV), and young rosemary (YR) groups). Then, we examined the number of intact neurons, myelin base protein (MBP), white matter (WM), levels of malondialdehyde (MDA), and glutathione peroxidase (GPx) in the PFC.

Results: The results showed that in the old vehicle rats compared to the young group without treatment, except for the MDA level (which increased), other variables significantly decreased (P≤0.05). Additionally, RE consumption demonstrated a significant elevation of WMA, MBP intensity, number of intact neurons, and GPx activity level, while MDA levels significantly reduced in the treated old rats compared to the old vehicle group (P≤0.05). However, there was no significant difference between the OR and YV groups (P≥0.05).

Conclusion: Overall, it seems that RE can protect and improve aging damages in the PFC due to its anti-oxidant properties. So, the use of RE can be a suitable strategy to prevent aging complications in the brain.