Iranian Journal of Basic Medical Sciences
Volume:28 Issue: 5, May 2025

Cancer is considered a serious threat to human life and one of the major leading causes of death in the world. As a critical medical challenge in developing and developed countries globally, progress in the design of theranostic nanomedicine is associated with the control of temporal-spatial variability, enhancing the site-specific therapy, and reducing the toxicity to normal tissue. As the primary noninvasive cancer treatment technique, photothermal therapy through radiation absorption in the near-infrared region generates hyperthermia for the ablation of cancerous cells. Photothermal therapy combined with other therapeutic techniques, including chemodynamic, photodynamic, and sonodynamic, has synergistic and enhanced effects on cancer therapy. Nanozymes, as intrinsic multienzyme mimics, can be robust cancer nanotherapeutics owing to the dual effect of catalytic functions and physicochemical advantages of nanomaterials. Nanozymes possess remarkable stability, precise penetrability, exceptional specificity, outstanding recoverability, and minimal toxicity. These attributes make them immensely powerful for therapeutic applications. In light of the significance of multifunctional nanozymes and their increasing focus on catalytic therapy for cancer tumors through reactive oxygen species (ROS), we have compiled a comprehensive overview of recent advancements in various photothermal-based assays utilizing nanozymes. Notably, our analysis reveals that incorporating nanozymes in PTT enhances the generation of ROS, leading to improved therapeutic efficacy against the tumor. In summary, this comprehensive overview highlights the significance of multifunctional nanozymes in advancing photothermal-based assays for cancer treatment. The findings underscore the potential of these innovative approaches to improve treatment precision and effectiveness while reducing adverse effects on healthy tissues.

Despite advancements in antimicrobial and anti-inflammatory treatments, inflammation and its repercussions continue to pose a considerable challenge in medicine. Acute inflammation may cause life-threatening conditions like septic shock, while chronic inflammation leads to tissue degeneration and impaired function. Lipopolysaccharides (LPS), a well-known pathogenic trigger contributing to several dysfunctions, is a crucial part of the outer membrane of gr-negative bacteria. LPS are well-known for eliciting acute inflammatory responses by activating a pathogen-associated molecular pattern (PAMP), which stimulates the innate immune system and triggers local or systemic inflammatory responses. LPS also activate numerous intracellular molecules that modulate the expression of a wide range of inflammatory mediators. These mediators subsequently initiate or exacerbate various inflammatory processes. Beyond immune cells, LPS can also activate non-immune cells, leading to inflammatory reactions. These excessive inflammatory responses are often detrimental and typically result in chronic and progressive inflammatory diseases, including neurodegenerative, cardiovascular diseases, and cancer. This review delves into the mechanisms by which the bacterial endotoxin LPS contribute to multiple inflammatory diseases. These insights into LPS signaling pathways could inform the design of new treatment strategies such as TLR4, NLRP3, HMGA1, MAPK, and NF-kB inhibitors. This enables precise targeting of inflammation-related processes in disease management.

This study aimed to evaluate the protective effects of shilajit on 5-fluorouracil (5-FU)-induced nephrotoxicity in a rat model.

Twenty male Sprague Dawley rats were divided into four groups: Control, 5-FU, shilajit, and 5-FU + shilajit. 5-FU was administered intraperitoneally at 200 mg/kg, while shilajit was given orally at 200 mg/kg. Kidney tissues were analyzed for oxidative stress markers, protein expression (SIRT2, SIRT3, β-catenin, E-cadherin, and caspase-3), and histopathological changes.

5-FU significantly increased oxidative stress parameters and kidney damage markers. Shilajit co-administration with 5-FU reduced oxidative stress and increased anti-oxidant status and SIRT2, SIRT3, and cell adhesion protein expression. Histopathological evaluation showed reduced renal damage in the shilajit + 5-FU group compared to the 5-FU group.

Shilajit exhibited significant protective effects against 5-FU-induced nephrotoxicity, improving oxidative parameters, protein expression, and kidney histopathology. Further studies are needed to elucidate its molecular mechanism and therapeutic potential.

Type 2 diabetes (T2D) represents a complex and multifactorial disorder, and efforts to discover its treatment are necessary. Browning of white adipose tissue (WAT) as a therapeutic target for diabetes seems to be induced by exercise through neuropeptide FF (NPFF) signaling in the hypothalamus and adipose tissue. This study aimed to explore the role of endurance training on the browning of WAT by assessing the expression of the gene and protein of NPFF and its receptors in the hypothalamus and adipose tissue.

Forty adult male Wistar rats were assigned into four groups: control, exercise, diabetic control, and diabetic exercise. The serum levels of lipid profile, insulin, and glucose, along with the expression of gene and protein of NPFF and its receptors (NPFFR1 and NPFFR2), were evaluated in the hypothalamus and adipose tissue. A histological examination was performed to evaluate the browning of WAT.

Metabolic parameters notably increased in the diabetic group. The gene and protein expression of NPFF and its receptors significantly decreased in the hypothalamus and fat tissue in the diabetic group. However, these changes in the hypothalamus, not in the adipose tissue, were significantly improved in the diabetic-exercise group compared to the diabetic group. The high WAT content in diabetic rats was decreased by exercise, leading to an increase in the browning of WAT.

Endurance progressive training could centrally, not peripherally, promote the browning of WAT in diabetic rats by enhancing the expression of gene and protein of NPFF and its receptors in the hypothalamus.

The use of cryoablation for colorectal liver metastases (CLM) remains limited and controversial. This study aimed to investigate the antitumor immune response following cryoablation combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment in a CLM mouse model.

A CLM mouse model was established using BALB/c mice. The tumor-bearing mice were randomly divided into Control group, GM-CSF group, cryoablation group, and cryoablation + GM-CSF group. Tumor size, survival time, dendritic cells (DCs) count, serum cytokine levels (IL-4, IFN-γ), and the Th1/Th2 ratio (IFN-γ/IL-4) were compared among the four groups.

The combination of cryoablation and GM-CSF demonstrated synergistic effects, resulting in the smallest tumor lesion, longest mean survival time, and highest DC count on day 21 post-treatment compared to other groups. Both cryoablation alone and combined with GM-CSF significantly increased serum IFN-γ levels and suppressed IL-4 levels on day 21 compared to pre-treatment levels (P<0.05). Notably, the combination of cryoablation and GM-CSF significantly elevated the Th1/Th2 ratio (P<0.05).

Combining cryoablation with GM-CSF treatment holds promise for CLM management. It exhibits increased DC infiltration within the tumor microenvironment, enhanced immune responses, and prolonged survival in tumor-bearing mice.

Colorectal cancer is one of the deadliest cancers worldwide, which can be prevented and even cured by early diagnosis and more efficient treatment modalities. Comprehensive transcriptional analysis has highlighted the importance of lncRNAs in CRC tumorigenesis. In this study, we identified co-expressed lncRNA networks based on public RNA sequencing data for biomarker prediction in CRC and then verified the best candidate experimentally. 

Publicly available RNA-sequencing data (BioProject PRJEB27536) of CRC samples and normal adjacent tissues were reanalyzed using the DESeq2 package in R to find differentially expressed lncRNAs. Pathway enrichment and gene network analysis were accomplished using GSEA and WGCNA to identify potential functions of lncRNAs with possible roles in tumorigenesis pathways. Subsequently, the expression of RP11-109D20.2 (lnc-Duox2-1:1) was assessed in fresh/frozen tissues obtained from 46 CRC patients by quantitative RT-PCR. 

A total of 17939 DElncRNAs were identified between CRC and normal tissues via bioinformatics analyses. A significant up-regulation of RP11-109D20.2 (48%) was observed in CRC samples. Functional enrichment analysis showed that RP11-109D20.2 was mainly related to pathways like phosphoric ester hydrolase, oxidoreductase, phosphoric diester hydrolase, and cyclic-nucleotide phosphodiester activities. Moreover, elevated expression of DUOX2 in tumors with high levels of RP11-109D20.2 suggests a link between these genes.

Our data revealed that RP11-109D20.2 may have a considerable role in CRC progression. However, further functional analyses are essential to evaluate the probable role of RP11-109D20.2 as a potential diagnostic marker and its potential role in the dysregulation of cyclic nucleotide phosphodiesterase genes in CRC.

Myocardial ischemia/reperfusion injury (MIRI) is the primary pathological injury following ischemic cardiomyocyte therapy, but there are few effective treatments available for MIRI. Apigenin (API) is an active ingredient of herbal medicine. Our study aims to verify whether API regulates autophagy and apoptosis against MIRI via miR-448/Sirtuin-1 (SIRT1) axis.

MTT, SOD, and LDH assays were used to measure cell viability, oxidative stress injury, and cell damage, respectively. RT-qPCR, western blot, and ELISA were used to measure RNA and protein expression levels.

Compared with the control group, cell viability and SOD levels in the cells of the OGD/R group were significantly decreased, LDH release in the cells was significantly increased, the level of miR-448 in the cells was significantly increased, the levels of SIRT1 mRNA and protein in the cells were significantly increased, the expression of LCII/I and Bcl-2 proteins in the cells were significantly down-regulated, and the expression of p62, Bax proteins in the cells and caspase-3 protein in the cell supernatant were significantly up-regulated. Compared with the OGD/R group, the above indicators were significantly reversed in the OGD/R+API group and the OGD/R+miR-448 inhibitor group. Compared to the OGD/R+miR-448 inhibitor group, the above indicators were significantly reversed in the OGD/R+miR-448 inhibitor+EX527 (SIRT1 inhibitor) group. Compared to the OGD/R+API group, the above indicators were significantly reversed in the OGD/R+API+miR-448 mimic group, OGD/R+API+EX527 group, and OGD/R+API+CA-5f (autophagy inhibitor) group.

API regulates autophagy and apoptosis via the miR-448/SIRT1 axis against MIRI.

The current work aimed at studying the impact of royal jelly on kidney damage caused by rhabdomyolysis in male rats.

40 male rats were randomly assigned to five groups of eight: control, rhabdomyolysis, and rhabdomyolysis, administered with three doses of royal jelly (RJ) (100, 200, and 400 mg/kg) for seven days. On the fifth day, we injected glycerol intramuscularly to induce rhabdomyolysis. Researchers examined serum biochemical parameters, inflammation, oxidative stress, apoptosis, and kidney tissue injury.

As a result of injecting glycerol, serum levels of creatinine, urea, and creatine phosphokinase were considerably elevated. The concentration of inflammatory mediators, as well as the expression of apoptotic parameters, was significantly elevated after glycerol injection. The percentage of kidney tissue damage and neutrophil gelatinase-associated lipocalin expression also increased significantly. Oral usage of RJ (100, 200, and 400 mg/kg) caused a decline in serum CPK, tissue level of total thiols, catalase activity, and renal expression of   BAX compared to the rhabdomyolysis group. Serum creatinine and NGAL expression were also significantly reduced by the RJ (200 and 400 mg/kg). RJ significantly reduced the concentration of inflammatory mediators at 100 and 200 mg/kg doses and the expression of bcl2 by RJ at 100 and 400 mg/kg doses.  

Royal jelly safeguards the kidney from rhabdomyolysis-related damage, primarily through its anti-oxidant, anti-apoptotic, and anti-inflammatory effects.

Sepsis, a severe consequence of infection leading to organ failure, incites damage in frequently affected brain tissue through inflammation and oxidative stress. This study aimed to assess the effectiveness of amantadine, an N-methyl-D-aspartate (NMDA) receptor antagonist, in mitigating sepsis-induced brain damage.

Thirty-two Wistar albino male rats were allocated into four groups: control, LPS (lipopolysaccharide 5 mg/kg, intraperitoneal, single-dose), LPS + amantadine, and amantadine alone. Six hours post-LPS administration, rats were euthanized under anesthesia. The neutrophilic infiltration and necrosis reaction were assessed in lung tissues through histopathological analysis, while expressions of interferon-alpha (IFN-α), caspase-3 (Cas-3), and Tumor necrosis factor-alpha (TNF-α) were examined using the immunohistochemical method. Levels of biochemical total anti-oxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were evaluated via the ELISA method. IL-1β, Cas-1, NLRP3, and IL-18 were evaluated via real-time qPCR.

The LPS group exhibited histopathologically significant hyperemia, increased septal tissue thickness, hemorrhage, and inflammatory cell infiltrates, and increased IFN-α, Cas-3, TNF-α immunohistochemical expressions, and IL-1 beta, IL-18, NLRP3, and Cas-1, gene expressions compared to the control group. All these findings were significantly reversed with amantadine treatment.

The pathophysiology of brain damage due to systemic inflammation is complex. Our findings suggest that amantadine reduces neuronal injury in the brain by alleviating oxidative stress and inflammation. Notably, amantadine’s efficacy appears to extend beyond NMDA receptors, implicating involvement in alternative pathways, such as Cas-1 activation by the NLRP3 inflammasome.

Spinal cord injury (SCI) is a highly disabling and fatal disorder with no effective treatment to date. Selegiline, a selective MAO-B inhibitor, has shown new neuroprotective and neurorescuing effects with various beneficial effects on neuron-associated disorders. These effects have triggered investigations into its impact on different neuron-associated disorders and SCI. Thus, in continuation of the previous studies, this study evaluates the local therapeutic effects of selegiline-loaded alginate hydrogel on SCI by analyzing apoptotic factors, histological factors, and improvements in locomotor function and neuropathic pain.

Hydrogels were fabricated via cross-linking gelation method and characterized by FT-IR and SEM analysis. Selegiline release from hydrogels was evaluated by UV spectroscopy, and hydrogel biocompatibilities were verified through an MTT assay. Afterward, 36 rats were divided into six groups: sham, negative group, treated with empty hydrogel, and three selegiline-treated groups (2.5, 5, and 10 mg/kg). After 28 days, the locomotor activity, the expression of Bax and Bcl2 (apoptosis index), and GFAP changes in the lesion site were assessed using Basso, Beattie, and Bresnahan (BBB) scale, western blot technique, and immunohistochemical assay, respectively.

Hydrogel tests showed the suitability of hydrogels and sustained selegiline release from them. Rats treated with selegiline-loaded hydrogels showed significant locomotor improvement and reduced apoptosis indices in SCI-induced rats (P≤0.05). Additionally, GFAP immunohistochemistry analysis indicated notable histological improvements. 

Findings suggest that selegiline-loaded hydrogels can improve SCI through apoptosis inhibition and neurorescuing effects. Further clinical studies are warranted to validate these findings in human SCI.

Liver fibrosis (LF) is a critical stage in chronic liver disease progression, and effective therapeutic drugs are currently lacking. Tanshinone IIA (Tan IIA), a monomer extracted from Salvia miltiorrhiza, shows potential in treating LF. This research aims to discuss the antifibrotic efficacy and underlying pharmacological mechanism of Tan IIA. 

The in vivo model was induced with CCl4 to form a LF model in mice, and the in vitro model was induced by TGF-β1 in LX-2 and HSC-T6 cells. Liver pathology was characterized by HE, Masson, and Sirius red staining, and serum levels of ALT, AST, LDH, and γ-GT were examined. Cell viability and proliferation were detected by Cell Counting Kit-8 and colony formation assays. Cell cycle distribution was detected by flow cytometry. The protein levels of p-ERK, cyclin D1, CDK4, and p-Smad3L were assessed through Western blot, immunohistochemistry, or immunofluorescence assays.

Tan IIA markedly decreased serum levels of ALT, AST, LDH, and γ‐GT. Collagen I and α-SMA were reduced, as shown by in vitro and in vivo models. Moreover, while arresting HSCs in the G1 phase was increased, Tan II A markedly inhibited cell viability and colony formation. Mechanistically, Tan IIA decreased the expression of p-ERK, cyclin D1, CDK4, and p-Smad3L proteins in TGF-β1-activated cells and CCl4-induced mice.

Tan IIA may improve LF by regulating the signaling axis of ERK/cyclin D1/p-Smad3L, thereby blocking activated HSCs in the G1 phase and inhibiting their proliferation.

Glycation is one of the primary underlying processes attributed to senescence and related diseases. No medicine currently targets this harmful manifestation. Drug repurposing is an efficient and cost-effective way of developing drugs. The present study evaluated meloxicam, a clinically used NSAID, for its ability to offer protection against glycative stress.

Methylglyoxal (MGO; 17.25 mg/kg) was administered for two weeks to create a rat model of glycative stress. Aminoguanidine (AG; 50 mg/kg) and Meloxicam (MEL; 0.15, 0.3, and 0.6 mg/kg) were used as standard and test agents, respectively. Afterward, the cognitive (Morris Water Maze), liver (LFT), and kidney (Creatinine) functioning were evaluated. The expression of genes of interest (TNF-α, RAGE, BACE, Glyoxalase, and VEGF) were estimated (qPCR) in the liver, brain, and kidney along with histopathology (H&E staining). Carboxymethyllysine (CML) levels in rat plasma were evaluated via ELISA.

MEL treatment has significantly (P<0.05) protected the MGO-induced cognitive (duration in target quadrant, time taken to get to target quadrant, and the frequency of crossings via platform location), hepatic, and renal impairment. The qPCR data revealed that MEL prevented MGO-induced enhancement in the expression of genes of interest. Additionally, the CML levels were significantly (P<0.005) normalized by concomitant administration of MEL. Histopathological examination did not reveal any remarkable outcomes.

MEL has significantly mitigated the rats’ MGO-induced cognitive, liver, and kidney impairments. Hence, it appears to be a potential molecule for repurposing as an antiglycation agent.

Cyclophosphamide (CP) is a chemotherapeutic drug used to treat various tumors. It causes nephrotoxicity by producing reactive oxygen species. Sinapic acid (SA) exhibits anti-oxidant, antiapoptotic, and anti-inflammatory activities at low doses as a phenylpropanoid. This study aimed to investigate the protective effects of SA on SP-induced renal injury. 

Forty-eight BALB/c mice were randomly divided into control, SA (for seven consecutive days, with two doses of 5 and 10 mg/kg), CP (single dose, 200 mg/kg), and CP + SA (5 and 10 mg/kg). On the 10th day of the study, mice were examined by renal function markers (Urea and Creatinine), oxidative stress markers (MDA and GSH), histopathological, and immunohistochemical assays (caspase-3 and NF-kB kidney). 

MDA levels increased and GSH levels decreased significantly in CP-treated mice. In addition, the histopathological structure of the kidney tissue in CP-treated mice showed significantly severe kidney tissue damage associated with increased urea and creatinine. The administration of SA in CP-treated mice significantly reduced serum urea and creatinine concentrations. In addition, the immunohistochemical staining of caspase- 3 and NF-kB decreased significantly in the CP + SA group compared to CP-treated mice. 

Overall, our study suggests that sinapic acid, a substance with antioxidant, antiapoptotic, and anti-inflammatory properties, can be used as a complementary therapy to protect nephrotoxicity against CP.

To investigate the ameliorative effects of Garcinia kola ethanol extract (EGK) on type 2 diabetes mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) and to explore its underlying mechanisms. 

In vivo, a T2DM rat model was established using HGHFD/STZ. In vitro, HepG2 cells were induced with FFA to create a model of lipid accumulation. Lipid accumulation (LA), oxidative stress (OS) levels, and inflammatory markers were measured using kit methods. Additionally, the expression of the SREBP-1c pathway was detected by immunohistochemistry and western blot (WB) to further understand the potential mechanism of EGK’s protective effect on diabetic liver injury. 

In vivo, EGK significantly reduced blood glucose levels (P<0.01), restored body weight (P<0.01), and improved liver LA, OS, and inflammatory levels (P<0.01) in diabetic rats. Histopathological results indicated that EGK effectively ameliorated diabetes-induced liver injury. Immunohistochemistry and WB results revealed that EGK significantly down-regulated the expression of the SREBP-1c pathway (P<0.01). In vitro, EGK markedly improved lipid accumulation, oxidative stress, and inflammation levels in HepG2 cells (P<0.01). Immunofluorescence and WB results showed that EGK significantly reduced the expression of the SREBP-1c pathway (P<0.01). 

EGK alleviates T2DM combined with NAFLD by reducing lipid accumulation through the inhibition of oxidative stress, inflammatory responses, and the SREBP-1c signaling pathway.

One of the leading causes of endometriosis is the return of menstrual blood flow into the pelvic cavity and the establishment of menstrual blood mesenchymal stem cells (MenSCs) outside the uterus. MenSCs from endometriosis patients (E-MenSCs) and healthy women have been shown to vary in terms of surface markers and gene expression, which may suggest the involvement of these cells in the development and expansion of ectopic lesions. This study aimed to investigate the effects of beta-catenin signaling inhibitor C-82 and naringenin as PI3K signaling pathway inhibitors on E-MenSCs to modulate their gene expression and functional pattern. 

Briefly, E-MenSCs isolated by density-gradient centrifugation were treated with C-82 and naringenin, and the genes and pathways related to inflammation, proliferation, and survival were evaluated. E-MenSCs showed increased early apoptosis and decreased levels of ROS, IL-6 and IL-8, ER, α-SMA, and Ki-67 protein expression. 

Our results shed light on the function of C-82 and naringenin in modulating E-MenSCs. 

However, more research is needed to analyze the precise effects of small molecule C-82 and naringenin on endometriosis.