Journal of Advances in Medical and Biomedical Research
Volume:31 Issue: 149, Nov-Dec 2023

Neuropathic pain (NP) is the outcome of lesion or disease of the nervous system, and it substantially influences the quality of life. Various inflammatory diseases such as rheumatoid arthritis (RA) and even cancer, may cause NP. Today, treatment of NP is the biggest pharmacological hurdles. Targeting inflammation is a broad task, since many mediators are involved in onset of particular disease. Among these many mediators, the reactive oxygen and nitrogen species generated by macrophages and neutrophils are of great interest because of their major contribution in development of inflammation and NP. This review will concentrate on the pathogenesis of inflammation based on involvement of reactive oxygen and nitrogen species and the activation of signalling cascades in response to oxidative stress. A systematic, and comprehensive search was conducted in the database. Based on the inclusion criteria, more than 300 peer-reviewed publications and 200 articles were chosen. In this review, data on oxidative stress and inflammation is compiled and discussed in the context of chronic neuropathic pain.It is suggested that oxidative stress can activate a variety of pro-inflammatory factors involved in chronic diseases. Animal and clinical evidence suggests that oxidative stress and inflammation linked to overproduction of ROS are highly likely to represent a critical factor for the development of NP in inflammatory diseases.

 Lung transplantation is a promising  therapy for patients with end-stage lung disease. Pulmonary surfactant is a lipid and protein complex which has  a key role in lung function. Molecular mechanisms mediating in rejection of lung transplantation related to surfactants are not still comprehensively understood. In this study, we applied bioinformatics approaches to identify genes and molecular mechanisms involved in surfactant function in rejection of lung transplantation.

 At first, transcriptomics data was extracted and analyzed to construct the protein-protein interaction network and gene regulatory network using Cytoscape. Then, networks analysis were performed to determine hubs, bottlenecks, clusters, and regulatory motifs to identify critical genes and molecular mechanisms involve in surfactant function in rejection of lung transplantation. Finally, critical genes selected for repuposing drugs.

 Analyzing the constructed PPIN and GRN identified SCD, FN1, ICAM1, ITGB8, FOXC1, SIX1, FHL2, KRT5, TFAP2A, GAS5, MALAT1, and lnrCXCR4 as critical genes. Enrichment analysis showed the genes are enriched for pulmonary surfactant metabolism dysfunction, defective CSF2RB causes pulmonary surfactant metabolism dysfunction 4 and 5, Interleukin-4 and Interleukin-13 signaling  may be the mechanisms for surfactant function in rejection of lung transplantation. We predicted some candidate drugs for preventing of lung transplantation rejection such as Sunitinib, Gemcitabine, Oxaliplatin, Hyaluronic acid, … .

 Following our model validation using the existing experimental data, our model suggested critical molecules and candidate medicines involve in  surfactant function in rejection of lung transplantation for furtur investigations.

 The reduction of dorsal hump in rhinoplasty can result in significant cosmetic and functional compromise if appropriate supports, such as a spreader graft or flap is not provided. However, if the hump reduction is slight, the function of enhancing maneuvers cannot be defined with certainty. This study aimed to assess the aesthetic effects of spreader graft placement in the patients with less than 3 mm hump reduction.

 This study was a double-blind clinical trial with 30 patients who were randomly divided into 2 equal sized groups. For patients in the control group, there were no augmentation techniques used during hump reduction; however, in the intervention group, spreader grafts were applied after hump reduction. After 6 months, the incidence of depression, step, narrowing, widening and asymmetry in dorsum was ascertained. Besides, the patients were asked to rate their satisfaction with their nasal dorsum aesthetics.

 Only one patient in the control group had an inverted-V deformity, and patients in the intervention group were more satisfied with the aesthetic results. These variations are clinically important even if they were not statistically significant.

 Using a spreader graft in the primary rhinoplasty of patients with less than 3mm hump reduction, without causing serious complications, increases the patient’s satisfaction with dorsum aesthetics.

 High power laser therapy (HPLT) seems to be a new modality to possibly manage rotator cuff tendinitis.The purpose of this study was to investigate the effects of HPLT on clinical and sonographic findings in people with chronic rotator cuff tendinitis.

 Thirty-two people suffering from rotator cuff tendinitis participated in this study. The patients  were  randomly assigned to the control group (n=16) that received routine physiotherapy including Transcutaneous electrical nerve stimulation (TENS), ultrasound, hot pack, exercise consisting range of motion, pendulum, strengthening, and stability exercises, or the treatment group (n=16) that received routine physiotherapy and HPLT in the painful area of the shoulder (12 sessions) Clinical and functional findings including pain, shoulder range of motion, shoulder disability, and sub-acromial liquid were measured using the visual analog scale, goniometry, questionnaire, and sonography, respectively before and after treatment.

 Pain, active and passive range of motion, shoulder disability and sub-acromial fluid accumulation were significantly different in both groups and improved, but no difference was reported in the thickness of the rotator cuff tendon, especially the supraspinatus tendon. The improvement was more significant (pain reduction and sub-acromial liquid, increase in range of motion and level of function) in the treatment group than in the control group (P <0.05).

 HPLT combined with the routine physiotherapy improve the clinical as well as sonography findings including supraspinatus tendon thickness and accumulation of sub-acromial fluid in people with rotator cuff tendinitis compared with those in the control group.

 Rheumatoid Arthritis (RA) is an autoimmune-driven chronic systemic inflammatory disease. It could result in miscarriage, pre-eclampsia, and preterm labor, among other unfavorable pregnancy outcomes. Thus, this study was conducted to investigate the adverse pregnancy outcomes in pregnant women with RA.

 Two cohorts of pregnant women with and without RA referred to the Ayatollah Mousavi Hospital's Gynecology and Obstetrics Clinic in Zanjan, Iran, during 2019-2020 were enrolled in a retrospective matched cohort study. Using their medical records, each participant completed a checklist of study variables. We used binary Logistic regression, chi-square test, Analysis of Variance, and independent samples t-test to analyze data using SPSS v.23.

 The study included 280 pregnant women. The mean age of the RA and control group (pregnant women without RA) was 32.4 ± 6.6 and 29.5 ± 6.7 years, respectively. The most prevalent adverse outcome was spontaneous abortion (54, 19.28%), which was significantly higher in the RA group (25% vs. 13.6%, P= 0.015). Cesarean section (24.3% vs. 10.7%, P= 0.003) and low birth weight (LBW) were both significantly higher in the RA group (15% vs. 5%, P= 0.005). RA increased the probability of spontaneous abortion, cesarean section, and LBW by more than 1.3 (odds ratio, 1.38; 95% CI, 0.45-5.46; P= 0.017), 2.2 (odds ratio, 2.24; 95% CI, 1.29-6.54; P =0.004), and 2.6 (odds ratio, 2.67; 95% CI, 1.86-7.05; P= 0.008) times, respectively.

 Pregnant women with RA are more likely to experience spontaneous abortion, cesarean section, and having LBW infants comparing to pregnant women without RA.

 Traditional economic studies on substance use disorder treatment have generally focused on the standard evaluation of the costs and benefits of treatment programs.  Meanwhile, willingness to pay (WTP) as a subjective economic indicator uncovers the intangible benefits of treatment that are not gauged by traditional measurements. This study aimed to examine the effect of cost payers’ income and substance use disorder severity on WTP for treatment.

 In an applied descriptive-correlational study, the Addiction Severity Index was used for patients with substance use disorder in two treatment settings: methadone maintenance treatment (MMT) and abstinence-based residential facilities (RFs). The cost payers’ WTP was measured by the contingency valuation method. The cost payers' income and the patients' addiction severity indexes were analyzed in relation to WTP in a regression model. We also used Kruskal-Wallis and Mann-Whitney U statistical tests to examine the differences in the two treatment settings.

 In MMT clinics, WTP increased with higher income and a higher substance use index, respectively. WTP decreased with the worse grades in the patients' legal and medical status. In RFs, however, changes in WTP for treatment were solely dependent on the cost payers’ income.

 When clients and their families bear the full cost of treatment, cost payers' income plays a key role in preparedness for purchasing treatment services. The severity of substance use disorder is the second factor determining WTP for treatment.

 Heat shock proteins (HSPs) have garnered significant interest as a potential host factor in COVID-19. By exerting control over HSP levels, the invading virus can effectively manipulate the destiny of host cells, capitalizing on their essential roles in cellular pathways and viral life cycles. Within this investigation, we present novel findings elucidating the variations in HSP27 protein and mRNA expression between patients exhibiting mild symptoms and those manifesting moderate-to-severe symptoms of COVID-19, juxtaposed against a control cohort.

 A total of 102 patient samples were included in the study, comprising 54 individuals with moderate-to-severe COVID-19 symptoms and 48 with mild symptoms. Additionally, 42 samples from healthy individuals constituted the control group. HSP27 protein levels were quantified using ELISA, while the transcript content was assessed using Real-Time PCR.

 Our initial findings revealed a statistically significant reduction in serum HSP27 levels among patients displaying mild COVID-19 symptoms when compared to the control group (P< 0.05). Nonetheless, this disparity did not achieve statistical significance in patients with moderate-to-severe symptoms. In contrast, the transcriptomic profile of HSP27 exhibited striking similarity across all groups, including mild, moderate-to-severe, and controls (P=0.25 and P=0.56, respectively).

 The present study, to date, is the first to investigate HSP27 gene expression levels in COVID-19 patients. Conducting further studies on HSP27 is of considerable help to clarify the importance of this molecule in SARS-CoV-2 infection.

 Acute myeloid leukemia (AML) has a complex course of treatment, including chemotherapy and bone marrow transplantation, which mostly results in drug resistance and recurrence. Therefore, alternative therapies have attracted the attention of researchers. Mesenchymal stem cells exert their paracrine effects through the secretion of multiple cytokines and vesicles. Recent findings suggest the possible antitumor properties of MSCs by the secretion of micro-vesicles, and consequent activation of cell death pathways in cancer cells. The present study evaluated how micro-vesicles from human placental mesenchymal stem cells affect the autophagy and apoptosis pathways in AML.

 After isolation and culture, hPMSCs were identified through flow cytometry. The Bradford method was employed to determine the concentration of MVs. The properties of MVs were confirmed by transmission electron microscopy (TEM) and DLS. Next, the KG1 cell line was exposed to MVs at concentrations of 25, 50, and 100 μg/ml for 24 hours. Subsequently, apoptosis was assessed using an Annexin V-FITC/PI kit, and ROS activity was gauged through the utilization of H2DCFDA. The gene expression in the autophagy and apoptosis pathways was investigated by using the real-time PCR technique.

 After 24 hours of treatment, a rise in intracellular ROS accumulation and apoptosis was observed in all groups compared to the control group. The mean intracellular ROS accumulation at the concentrations of 25, 50, and 100 μg / ml of the samples and the control group was 62.21% (P<0.0002), 66.25% (P<0.0001), 62.55% (P<0.0001), and 26.1% (P<0.0001), respectively. The apoptosis indices at the concentrations of 25, 50, and 100 μg / ml of the samples were 62.6% (P<0.0002), 46.0% (P<0.0001), and 48.2% (P<0.0001), respectively. Furthermore, analyzing genes through RT-PCR indicated a considerable increase in the expression of autophagy-related and pro-apoptotic genes.

 Our findings indicate that hPMSC-MVs induce Cell death pathways of autophagy and apoptosis in the KG1 cell lines. Additionally, hPMSC-MVs exhibited heightened impactful anti-proliferative and pro-apoptotic outcomes on KG1 cells in vitro.

 Peganum harmala has emerged as a promising anti-diabetic medicine. There is no study regarding the impact of P. harmala concentration on the insulin secretion, C-peptide secretion, and glucose uptake. We investigated the effect of different concentrations of methanolic extracts of P. harmala seed and leaf on insulin and C-peptide secretion, and glucose uptake.

 After the cell passaging, pancreatic carcinoma cell line (PANC-1) and HT1080 were treated with different concentrations of seed and leaf extract of P. harmala, harmine, and ghrelin agonists. The MTT was employed to assess the cell survival at the selective doses, and using a spectrophotometer, the absorbance was determined at 570 nm. After 72-h treatment, the insulin and C-peptide secretion were measured by ELISA. To measure the intracellular glucose concentrations after treating muscle carcinoma cell lines, glucose oxidase method was utilized.

 P. harmala seed and leaf extracts increased the secretion of insulin and C-peptide in a dose-dependent manner compared to ghrelin and harmine. These extracts increased the intracellular glucose concentration at high doses (150 and 1500 µg/ml for the seed and leaf extract, respectively) of HT1080 cell line. However, their high concentration was toxic and reduced the cell survival. The methanolic extracts of seed showed a higher insulin (17.5-fold) and C-peptide (7.8-fold) secretion compared to the leaf methanolic extracts.

 Due to the presence of β-carbolines, the P. harmala seed extract has toxicity and affects insulin secretion and C-peptide uptake secretion at lower concentrations than those of leaf extract.

 Medulloblastoma formation is importantly related to granular cell proliferation and differentiation, processes which are under the influence of sonic hedgehog (SHH) signaling. Exons of genes encoding different components of this signaling pathway (e.g., ligands, co-receptor, transcription factors, and target genes) were investigated to identify the proper single guide RNAs for selective targeting of positive regulators of the SHH pathway.

 The genomic DNA sequences of corresponding genes of several positive regulators of the SHH pathway (in Homo Sapiens), including SHH, SMO, GLI1, GLI2, MYCN, and MYC, were retrieved from the National Center for Biotechnology Information (NCBI) gene database. Next, the exon sequences of these genes were identified using protospacer adjacent motif (PAM) of NGG and Streptococcus pyogenes Cas9 nuclease and evaluated by CRISPOR software to select the best sgRNA for each target gene.

 The analyses revealed the best sgRNAs for the SHH, SMO, GLI1, GLI2, MYCN, and MYC genes targeted exon 1, -4, -4, -5, -2 and -2, respectively. Proper sgRNAs for targeting each exon in each gene were also identified.

 This study revealed possible specific exonic targets of components of the SHH signaling pathway through designing proper sgRNAs using the CRISPR/Cas9 genome editing approach.

 Uncontrolled active rheumatoid arthritis patients have a progressive disability, pain, swelling problems, and stiffness that often lead to systemic complications, early death, socioeconomic costs, and comorbidity. The objectives of this study were to measure the serum levels of Tripartite motif-containing protein 72 in Iraqi patients with rheumatoid arthritis and healthy individuals, assessment of the efficiency of Tripartite motif-containing protein 72, determine their essential serum rates in association with disease activity,  sociodemographic and clinical specifications of the diseases.

 In this case-control study, 117 Iraqi patients with rheumatoid arthritis were investigated according to the 2010 American College of Rheumatology / European League Against Rheumatism from December 2020 to March 2022. The patients were divided into two groups. Group 1 were the RA patients with active disease, Group 2 were the RA patients with inactive disease, and healthy subjects served as the control group.

 Serum levels of Tripartite motif-containing protein 72 in the active RA groups (101.92±160.18 Pg/mL) were significantly higher as compared with the inactive RA group (64.58±54.34 Pg/mL) and the control group (41.06 ±32.48 Pg/mL) (P˂0.005). Tripartite motif-containing protein 72 could not discriminate between RA and the controls (since its AUC ≥0.689).

 There was a positive relationship between DAS-28ESR and Tripartite motif-containing protein 72 levels, which induces bone erosion. The serum Tripartite motif-containing protein 72 level showed a significant elevation in rheumatoid arthritis patients compared with healthy controls. Tripartite motif-containing protein 72 had a poor discriminative ability between RA and the control group.

Encephalopathy is a syndrome of overall brain dysfunction with unknown causes despite its well-recognized etiology. This study reports clinical laboratory, radiological, and magnetic resonance imaging (MRI) findings as well as whole-exome sequencing (WES) of a female patient aged 19 months and 7 days with encephalopathy. To this end, the documented files of the hospitalized encephalopathy patients in Ayat Allah Mosavi hospital (Zanjan, Iran), referred from Khodabandeh city, Zanjan, Iran, were investigated. The initial symptoms, laboratory tests, computerized tomography (CT) scans, MRI, WES, and the course of disease were reported. The laboratory examination revealed mild anemia, and the normal range of the CSF, ESR, and CRP. Brain CT indicated brain edema while the MRI analysis of the brain revealed hypersignality. The c. 352G>A heterozygote variant was diagnosed in the PPP2RIA gene in exon four of chromosome 19. According to the observations, the frequency of this disorder was higher in this region of Zanjan province than other areas. The limitation of this study such as lack of access to the patients or biological samples of other similar patients hindered further evaluation. Hence, comprehensive research must be conducted to reveal the underlying etiology.