Iranian Journal of Basic Medical Sciences最新文献

Objectives: Plinabulin, a marine-derived anticancer drug targeting microtubules, exhibits anti-cancer effects on glioblastoma cells. However, its therapeutic potential, specifically for glioblastoma treatment, remains underexplored. This study aims to elucidate the mechanisms by which plinabulin exerts its effects on glioblastoma cells.

Materials and methods: Using the SRB and colony formation assay to observe the effect of plinabulin on glioblastoma cell viability. Wound healing and transwell migration assay were used to test the effect of plinabulin on glioblastoma cell metastatic potential. Crucial target genes were identified through RNA sequencing and bioinformatics analysis. Protein levels were evaluated in a concentration-dependent manner using western blot analysis.

Results: Plinabulin suppressed glioblastoma cell proliferation by causing cell cycle G2/M phase arrest and inhibited migration. The IC50 values were 22.20 nM in A172 cells and 20.55 nM in T98G cells. Plinabulin reduced AKT and mTOR phosphorylation. Combined with the AKT/mTOR inhibitors LY294002 and rapamycin, plinabulin decreased p-mTOR and EGFR protein levels and increased cleaved-PARP levels. Plinabulin induces autophagy, and using an autophagy inhibitor enhances plinabulin-induced cell apoptosis. This suggests that plinabulin might trigger cytoprotective autophagy in glioblastoma cells. These findings indicate that plinabulin hinders glioblastoma growth and induces protective autophagy via the PI3K/AKT/mTOR pathway. Additionally, plinabulin combined with erlotinib showed greater cytotoxic efficacy than either drug alone in glioblastoma cells in vitro.

Conclusion: Our study provides new insights into the efficacy of plinabulin against glioblastoma and highlights the potential clinical utility of combining plinabulin with EGFR inhibitors as a chemotherapy strategy.

Objectives: This study aimed to investigate the potential effects of different doses of Lavender angustifolia essential oil (Lavender EO) administered by inhalation on sleep latency and neuromodulators regulating the sleep/wake cycle in rats with total sleep deprivation (TSD).

Materials and methods: Forty-eight male Sprague-Dawley rats were divided into five groups: Control, Alprazolam (ALP, 0.25 mg/kg given intraperitoneally), L1 (Lavender EO, 0.3 ml given by inhalation), L2 (Lavender EO, 0.5 ml given by inhalation), and L3 (Lavender EO, 1 ml given by inhalation); TSD was applied to all groups. Rats in SD groups were kept on a platform surrounded by water for 18 hr for 20 days, and for the remaining time, the animals were exposed to Lavender EO for 1 hr (11:00-12:00) and then were kept in their home cage for 5 hr (12:00-17:00). Their brain and brainstem were removed for histopathological and immunohistochemical analyses (c-Fos, ChAT, GAD, and ADRB2 expression) in the locus coeruleus (LC), basal forebrain (BF), and preoptic area (PO).

Results: The groups ranked by the severity of edema, hyperemia, and neurodegeneration in LC, BF, and PO areas were control, L3, L1, L2, and ALP. c-Fos expression significantly decreased in all brain regions in all groups except the L1 group. ChAT and GAD expressions increased dramatically in all brain regions. ADRB2 significantly increased in LC in ALP and L2 groups; in the PO area in ALP, L1, and L2 groups; and in BF in all groups.

Conclusion: Lavender EO treatment ameliorated c-Fos, ChAT, GAD, and ADRB2 expression, similar to the effect of ALP.

Objectives: In this investigation, the protective effects of hydroxytyrosol (HT) administered prior to myocardial infarction in rats were examined, with a particular focus on its potential roles within the Notch pathway.

Materials and methods: The animals were categorized into seven groups (n=7): control, myocardial infarction (MI) 6^th hr, MI 24^th hr, MI 7^th day, MI+HT 6^th hr, MI+HT 24^th hr, MI+HT 7^th day. In order to create infarction, the rats received a subcutaneous injection of isoproterenol at a dose of 200 mg/kg. Rats were given 4 ml/kg/day liquid containing HT orally for six weeks before infarction. Histopathological examination was conducted on heart tissue to assess Notch1, Hes1, and DLL4. Biochemical parameters were analyzed in serum using the ELISA method.

Results: The study revealed an increase in Notch1 and DLL4 levels, particularly at the 24^th hr and 7^th day after the occurrence of myocardial infarction. DLL4 increased at 24 hr and 7 days of infarction after HT administration compared to control. Hes1 levels increased towards the seventh day after infarction and following HT application before infarction. It was noted that the severity of histopathological damage in heart tissue was reduced at the 24^th hr of infarction in rats treated with HT prior to infarction. A significant decrease in fibrosis was observed on the seventh day of infarction in rats given HT before infarction. The levels of biochemical parameters decreased with the administration of HT before the occurrence of infarction.

Conclusion: HT is thought to exert a cardioprotective effect in MI, potentially mediated through the Notch pathway.

Objectives: To investigate the impact of Pentoxifylline (PTX) on the in vitro maturation (IVM) of mouse oocytes and its effect on oocyte quality.

Materials and methods: This experimental study involved culturing mouse oocytes in an IVM medium with varying PTX concentrations (0-100 μM). Post-culture, oocytes were assessed for nuclear and cytoplasmic maturation and quality indicators, including germinal vesicle breakdown (GVBD), first polar body extrusion (PB1E), cortical granules (CGs) distribution, spindle structure, chromosome alignment, and intracellular reactive oxygen species (ROS) levels.

Results: Treatment with PTX at 10, 25, and 50 μM concentrations significantly enhanced the nuclear maturation rates of oocytes. The optimal concentration was found to be 10 μM, as it resulted in the most favorable cytoplasmic maturation, characterized by improved distribution of CGs, spindle structure, and chromosome alignment. Additionally, treatment with 10 μM PTX effectively reduced reactive oxygen species (ROS) levels.

Conclusion: PTX supplementation at specific concentrations enhances mouse oocyte maturation and quality, potentially by facilitating CG distribution, spindle integrity, and chromosome alignment and by reducing ROS production.

Objectives: Rutin is a bioflavonoid compound renowned for its anti-oxidative, anti-inflammatory, and antinociceptive properties. The present study aims to assess its therapeutic efficacy on complete Freund's adjuvant (CFA)induced inflammatory pain.

Materials and methods: Arthritis was induced in Wistar rats via subcutaneous administration of CFA into the right hind paw. Rutin (15 and 30 mg/kg) and indomethacin (5 mg/kg, orally) were given once daily for three weeks. Parameters observed included alterations in paw swelling perimeter, arthritis scores, and body weight. Additionally, antinociceptive activity was measured through thermal hyperalgesia and cold allodynia responses. The Tumor necrosis factor-alpha (TNF-α) level in the serum was measured. Malondialdehyde (MDA), thiol levels, catalase, and superoxide dismutase (SOD) activities were also evaluated as serum oxidative stress markers.

Results: Rutin and indomethacin significantly suppressed alterations in paw edema, pain responses, and arthritis scores and reduced the loss of body weight in contrast to disease-control rats. Furthermore, in contrast to disease control rats, rutin and indomethacin treatment exhibited an anti-inflammatory effect through a marked reduction in TNF-α levels in the serum. Rutin and indomethacin demonstrated a significant increase in catalase and SOD activities, a total thiol level, and a decrease in MDA level compared to the disease-control rats.

Conclusion: These results suggest that rutin's antiarthritic effect is mediated by its antinociceptive, anti-oxidant, and anti-inflammatory properties.

Objectives: Rosmarinic acid (RA) is a herbal compound with various antioxidant and anti-inflammatory effects. This study aimed to explore the anti-inflammatory and anti-apoptotic properties of RA in folic acid-induced renal injury.

Materials and methods: Thirty-six male C57/BL6 mice were randomly divided into six groups (N=6): Control (received normal saline), NaHCO₃ (received NaHCO₃ as folic acid solvent), FA (received folic acid (FA)(IP) to induce renal injury), RA (received 100 mg/kg RA), RA50-FA (received 50 mg/kg RA solution after folic acid injection), and RA100-FA (received 100 mg/kg RA after folic acid injection). For ten days, the treatment groups received RA by gavage. The effects of RA were assessed using H & E staining, biochemical tests, western blotting, and ELISA in the kidney tissues of the mice. Real-time RT-PCR was also performed to evaluate the expression changes of renal genes.

Results: Our data showed that treatment by RA led to the over-expression of FoxO3 (P<0.05) and decrease in NFκB levels (P<0.01 and P<0.05) and expression of TNFα (P<0.05) and IL6 (P<0.001 and P<0.01). Other evaluations showed a decrease in p53 (P<0.01 and P<0.001), Bax/Bcl-2 ratio expression (P<0.01 and P<0.05), and Caspase-3 level (P<0.01 and P<0.05) compared to the folic acid group. Histological and biochemical results also confirmed the attenuation of tissue damage.

Conclusion: This study revealed that RA's positive effects on folic acid-induced renal injury might result from the involvement of the FoxO3/NFκB pathway, thereby suppressing inflammation and apoptosis.

Objectives: An ideal strategy to control acute or chronic toxoplasmosis can be the development and production of an effective vaccine. Liposomes as immunoadjuvants may be utilized to boost immune reactions for various antigens.

Materials and methods: In this study, we encapsulated soluble Toxoplasma antigen (SA) in 1, 2-Dioleoyl-3-trimethylammonium propane (DOTAP) liposomes to assess the elicited immunological response. BALB/C mice received three intramuscular injections of various formulations separated by two weeks. The kind of immune reaction that was created, the degree of protection, the percentage of BALB/c mice that survived the Toxoplasma gondii challenge, the immune reaction assessment with cytokine synthesis (IFN-γ, IL-4), and the titration of IgG isotypes were all evaluated.

Results: Compared to other groups, the liposome DOTAP + imiquimod + SA-immunized mice showed a significantly lower death rate (P<0.01). Liposome DOTAP + Imiquimod + SA had higher IgG2a and IFN-γ secretion levels than the control group (P<0.001 and P<0.0001, respectively).

Conclusion: According to the study's findings, the liposome DOTAP + imiquimod + SA formulation generates a cellular immunological response, making it resistant to the T. gondii challenge.

Objectives: Soybeans have various positive effects on health, including anti-inflammatory and preventing kidney damage. There is concern regarding the phytoestrogen content due to the high isoflavone content in soybeans. Various forms of soybean processing have been tried; in this study, the hydrolysis method will be used to obtain the active substance Arginine-Glycine-Aspartate (RGD) tripeptide in soybean protein hydrolyzed by bromelain (SPHB). The research aimed to determine the characteristics and influence of SPHB on kidney function, inflammation, body weight, and estrogen in male Wistar rats induced by gentamicin.

Materials and methods: Soybeans (Glycine max) are hydrolyzed using the proteolytic enzyme Bromelain from pineapples. The proteomics was investigated using Liquid-Chromatography Mass Spectroscopy Tandem (LC-MS/MS). SPHB in three doses would be tested for 28 days on male Wistar rats induced by gentamicin. The parameters measured were body weight, high-sensitive cell reactive protein (hs-CRP) levels, urea, creatinine, and estrogen levels.

Results: SPHB has a low molecular weight (LMW) of 10 kDa and contains RGD in the lunasin sequence. SPHB showed no effect on body weight (P>0.05). The impact of SPHB on hs-CRP, urea, and creatinine showed differences significantly from the positive control, especially SPHB at a dose of 112 mg/day (P<0.01). Meanwhile, SPHB has almost no effect on estrogen levels.

Conclusion: The administration of SPHB with LMW and contains lunasin showed decreased inflammation and kidney function parameters but did not affect body weight and estrogen levels in induced gentamicin Wistar rats.

Objectives: Anemoside B4 (AB4) is a multifunctional compound with anti-inflammatory, anti-apoptotic, antioxidant, antiviral, and autophagy-enhancing effects. However, the role of AB4 in cerebral ischemia/reperfusion injury (CIRI) remains obscure. This experiment aims to investigate the pharmacological effects of AB4 in CIRI.

Materials and methods: In vivo, eighty male SD rats were randomly divided into five groups: sham, MCAO/R, LD group (2.5 mg/kg), MD group (5 mg/kg), and HD group (10 mg/kg). The rats in sham and MCAO/R groups were given equal volumes of normal saline. In vitro, PC12 cells were divided into five groups: normal, OGD/R, OGD/R+AB4 (50 μM), OGD/R+AB4 (100 μM), and OGD/R+AB4 (200 μM). The cells were treated with hypoxia and hypoglycemia for 1.5 hr and reoxygenation for 24 hr.

Results: In vivo, TTC and neurological scoring tests indicated that AB4 favors promoting the recovery of the brain. The histopathologic study of the brain tissues revealed that AB4 inhibited the damage of neuron cells. The TUNEL assay found that AB4 could improve cell apoptosis and prevent the brain from injury. In vitro, the data showed that AB4 inhibited cell damage and prevented PC12 cells from OGD/R injury, reduced IL-1β content, and increased the IL-10 level. AB4 could inhibit apoptosis of PC12 cells, down-regulate Caspase 12 and BAX expression, and up-regulate Bcl-2 expression.

Conclusion: AB4 played a protective role in CIRI and could be a promising active ingredient against ischemia stroke.

Objectives: To explore the effects of puerarin on renal ischemia/reperfusion injury and the possible mechanism.

Materials and methods: The experimental mice were injected with puerarin (50 or 100 mg/kg) per day or equal sterile saline by intraperitoneal injection for one week, and a renal I/R injury model was constructed. HK-2 cells were incubated with puerarin (1 uM and 10 uM) before the H/R model. Immunohistochemistry, immunocytochemistry, and Western blot analysis were used to detect the protein associated with apoptosis and endoplasmic reticulum stress.

Results: Puerarin could improve renal function and attenuate tissue structural damage after renal I/R. Meanwhile, puerarin alleviated apoptosis and endoplasmic reticulum stress by decreasing expression levels of specific biomarkers such as caspase-3, GRP78, CHOP, and p-elF2α/ elF2α in animals and HK-2 cells. The up-regulated expression of Nrf2 and HO-1 protein after puerarin treatment indicated that the Nrf2/HO-1 signaling pathway might mediate the protective mechanism of puerarin against renal I/R.

Conclusion: Our results suggest that puerarin alleviated renal ischemia/reperfusion injury by inhibiting apoptosis and endoplasmic reticulum stress via the Nrf2/HO-1 pathway and offered new insights for preventing and treating renal I/R.