نشریه پژوهش در پزشکی
سال چهل و هفتم شماره 4 (پیاپی 188، زمستان 1402)

One of the concerns in assisted reproduction technology is recurrent implantation failure. The receptivity of uterine endometrium is considered as the main factor of implantation failure in assisted reproductive cycles. Decidua is a tissue originating from endometrial stromal cells, which main function is the initiation and maintenance of embryo implantation. Since the role of vitamin D has been shown in the processes of implantation and pregnancy maintenance, the present study aims to determine the serum level of vitamin D and its relationship with the expression and protein levels of the decidualization factors in women with recurrent implantation failure.

In this historical cohort study, among 36 eligible women with recurrent implantation failure, 12 women with vitamin D deficiency (less than 20 ng/ml) as the case group and 24 women with sufficient vitamin D (more than 30 ng/ml) ml) as the control group were included in the study. In the middle of the luteal phase, the endometrial biopsy was collected and assessed in both groups. The data are reported as mean ± standard deviation. Student's Man U Witny was used to compare the studied groups. P value less than 0.05 was considered statistically significant.

The results of Mann-Whitney-U test showed that the expression of IGFBP-1 (P = 0.0016), PRL (P = 0.004) and HOXA10 (P = 0.001) genes in the sufficient vitamin D group (1±  0.05, 1±  0.05, 1±  0.1 respectively) were significantly higher than the vitamin D deficiency group (0.5 ± 0.1, 0.5 ± 0.1, 0.4 ± 0.1 respectively). Also, the levels of IGFBP1 (P = 0.0001), PRL (P = 0.004) and HOXA10 (P = 0.036) proteins in the sufficient vitamin D group  (3.436 ± 0.05, 6.127 ± 1, 3.778 ± 1 respectively) were significantly higher than the vitamin D deficiency group (0.1196 ± 0.01, 2.185 ± 0.5, 0.4717 ± 0.01 respectively).

It seems VD deficiency may cause disturbances in gene expressions and protein levels of decidualization factors that are critical for embryo implantation.

The immune system is responsible for protecting the body against foreign and carcinogenic agents, and its weakness can lead to death. The genus Allium has been proposed as a suitable candidate for maintaining the homeostasis of the immune system, so in this study, we investigated the effects of hydroalcoholic extract of Allium jesdianum on various immune responses in mice.

In this experimental study, we investigated the effect of different doses (50, 100, and 200 mg/kg) of the hydroalcoholic extract of A. jesdianum on the immune system of 25 mice in four groups. Animal weight, spleen organ weight and their relative weight, blood lymphocytes, ability to produce antibodies by hemagglutination method, delayed hypersensitivity response, mitogenic power of lymphocytes using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) were investigated GraphPad Prism v9.5.0.730 x64 + v8.4.0.671 software was used for statistical calculations. Comparison between different groups was done using one-way ANOVA test and Tukey-Kramer posttest, and p > 0.05 was considered as a significant difference.

The results of this study show that A. jesdianum could not have an effect on the population of blood lymphocytes (p > 0.05) and general weight (p > 0.05), but the weight of the spleen (0.23 ± 0.22) and the relative weight of the spleen (0.96 ± 0.09) increased. Exposure to A. jesdianum caused a significant increase in the responses of the delayed hypersensitivity test after 24 hours (53.47 ± 8.27) and 48 hours (68.81 ± 11.34) compared to the control group. Also, A. jesdianum significantly increased the antibody titer compared to the control group (6.91 ± 0.17). In addition, A. jesdianum could increase the proliferation of spleen lymphocytes (7.71 ± 0.34). Also, at the doses of 100 mg/kg (1.49 ± 0.09) and 200 mg/kg (2.39 ± 0.12), it increased the proliferation response to LPS mitogen; while only at the dose of 200 mg/kg (2.46 ± 0.22) was able to increase the proliferative response to PHA mitogen.

It seems that A. jesdianum improves various factors of the immune system. Its effects include increasing the proliferation of spleen lymphocytes, delayed proliferative response, and antibody production. In general, A. jesdianum was able to strengthen various immune responses, including humoral immunity and cellular immunity.

The cerebellum is a part of the nervous system that is associated with motor coordination and balance control. Methadone is a centrally-acting synthetic opioid analgesic widely used in methadone maintenance therapy (MMT) programs throughout the world. Unfortunately, the abuse of methadone is currently spreading, and on the other hand, many deaths due to the use of this drug have also been reported. There is still no detailed information about the toxicity of this drug on the nervous system. Therefore, considering its neurotoxic effects, especially on the cerebellum, the aim of this study is to investigate histological changes in the cerebellar cortex associated with methadone administration.

This research is an experimental study. Twenty - four adult male albino rats were randomized into two groups of control and methadone treatment. Methadone was subcutaneously administered (2.5-10 mg/kg) once a day for two consecutive weeks. Stereology was used to evaluate the volume and number of cells in the cerebellar cortex, and immunohistochemistry was used against calbindin to evaluate the number of Purkinje neurons. Data analysis was done with Prism software and independent t-test.

The results of our study showed that administration of methadone decreased the volume of the molecular layer compared to the control group (P < 0.01) (P < 0.017, t = 5.37, Mean ± SEM = 1.429 ± 0.26) (the mean of the control group was 6.05 and the methadone group was 4.62). On the other hand, the number of Purkinje neurons in the methadone group showed a significant decrease compared to the control one (P < 0.05) (P < 0.016, t = 3.291, Mean ± SEM = 2264 ± 687.9) (the mean of the control group was 17826 and the mean of the methadone group was 15562). Our findings also showed that the volume of the granular layer (P < 0.04, t = 2.479, Mean ± SEM = 0.33 ± 0.825) (the mean of the control group was 4.375 and the mean of the methadone group was 3.55) and the volume of the white matter of the cerebellum in the methadone group showed a significant decrease compared to the control group (P < 0.02, t = 3.03, Mean ± SEM = 1.229 ± 0.404) (the mean of the control group was 3.28 and the mean of the methadone group was 2.06). In addition, the number of calbindin- positive neurons showed a significant decrease in the methadone group compared to the control group (P < 0.02, t = 2.68, Mean ± SEM = 2.68 ± 7.2) (the mean of the control group was 20.8 and the methadone group was 13.6).

These findings showed that methadone administration caused damage to the gray and white matter of the cerebellum. The death of Purkinje cells due to methadone can cause disturbances in cerebellar functions. It seems that the administration of methadone should be accompanied by more precautions.

Considering the roles of resistin, leptin and adiponectin in metabolic activities, especially in relationship with exercise and adipose tissue, and the lack of research in a related context this study was carried out to examine the effect of aerobic training and high-fat diet on leptin, adiponectin and resting serum levels of resistin in male rats.

This research was conducted using an experimental method. For this purpose, 28 male rats with an average weight of 152 ± 5g and the age of four weeks were divided into four groups: normal diet (N = 7), high-fat diet (N = 7), training (N = 7) and high-fat diet+ training (N = 7) groups. High-fat diet groups underwent high-fat diet (HF: 5/817 kcal/g) for 30 days. From the 60th day of life, a normal fat diet (NF: 3/801 Kcal/g) was applied Aerobic exercise wascarries out on a treadmill, for four weeks, three times a week (12 weeks from 60th to 98th days of life), 40 minutes with 50 cm/s speed. ELISA method was used to measure the biochemical markers including resistin, adiponectin and leptin. Factorial analysis of variance was used for statistical analysis. If post hoc comparisons were needed to compare groups two by two, Turkey’s post hoc test was used according to the results of Levine’s test.

The resultes showed that high fat diets cause a significant increase (p = 0/001) in serum levels of leptin (12/77 ± 1/12), leptin to adiponectin ratio (0/62 ± 0/13) and resistin (4/22 ± 0/58), and a decrease in (p = 0/01) adiponectin (21/12 ± 4/28) in male rats. However, aerobic exercise was accompanied by a significantdecrease(p = 0/003) in serum levels of leptin (6/17 ± 0/96), leptin to adiponectin ratio (0/14 ± 0/03), and resistin (2/42 ± 0/69). Moreover, an increase in (p = 0/001) adiponectin serum levels (42/74 ± 4/9) was observed.

Aerobic exercise might have beneficial effects on adiponectin, leptin, and leptin toadiponectin ratio in people with high-fat diet. On the other hand, high-fat diet is associated with detrimental effects on these cytokines and resistin.

Today, Thimerosal is used as a preservative in vaccines, pharmaceutical and ‎health products. There is limited and conflicting information about the effects of this ‎substance on the structure of cortical synapses. The aim of this study was to investigate the ‎effects of Thimerosal on genes and molecules involved in the structure and function of ‎synaptic connectivity, the number of astrocytes, and neurons in the prefrontal cortex of ‎male rats.

In this experimental study, 18 male rats were randomly divided into three groups: 1) experimental group receiving a dose of 3000 µg/kg Thimerosal on days 7, 9, 11, and 15 after birth, 2) solvent group receiving phosphate-buffered saline according to the same pattern, and 3) control group receiving no injection. In the fourth week after birth, samples from the prefrontal cortex were collected for immunohistochemical, histological, and molecular studies. One - way analysis of variance (ANOVA) and LSD test were used to determine statistically significant differences between the groups, and the data were expressed as Mean ± SD.

The results of this study revealed a significant decrease in the expression levels of Cadherin-8 (0.18 ± 0.079) and Synapsin-1 (0.36 ± 0.12) genes in the Thimerosal-exposed group compared to both control group (1 ± 0.01 for Cadherin-8 and 1 ± 0.009 for Synapsin-1) and solvent group (0.91 ± 0.097 for Cadherin-8 and 0.84 ± 0.10  for Synapsin-1) (p < 0.001). Furthermore, there was a significant decrease in the number of astrocytes in the Thimerosal - exposed group (10.66 ± 1.86) compared to the control group (6.43 ± 1.01) and the solvent group  (6.93 ± 1.39), as well as a decrease in the number of neurons (194.66 ± 19.59) compared to the control group (267.99 ± 10.19) and the solvent group (252.33 ± 23.06) (p < 0.01).

It seems that Thimerosal causes abnormal changes in the expression levels of genes ‎involved in the function and structure of synapses. Prolonged exposure to Thimerosal may lead to neurodevelopmental disorders.

Resistance to various antibiotics is one of the most problematic hospital complications and a mortality cause. Curcumin or diferuloylmethane is a strong antioxidant present in turmeric, and its antibiotic properties have attracted the attention of researchers. Also, this substance can penetrate other molecules. This research aims to investigate the synergistic effect of curcumin with three antibiotics rifampin, meropenem, and curcumin against Pseudomonas aeruginosa.

In this experimental study, curcumin was extracted at concentrations of 20, 40, 80, and 100 µg/ml. Antibiotics rifampin, meropenem, and amikacin were extracted at the same concentrations and their effect on the mean and standard deviation of the growth halo of Pseudomonas aeruginosa bacteria was investigated. Finally, a combination of antibiotics and curcumin in ratios of 75:25, 50:50 and 25:75 was made its effect on the mean and standard deviation of the halo diameter of non-growth of Pseudomonas aeruginosa bacteria was investigated. In this study, the Kolmogorov-Smirnov test was used to determine whether the data were parametric or non-parametric, and then, according to the results of the Kolmogorov-Smirnov test, the mean comparison test was used.

By increasing the ratio of curcumin and antibiotics, the mean and standard deviation of the diameter of the non-growth halo against Pseudomonas aeruginosa increased compared to the antibiotic alone (rifampin- curcumin       P-value = 0/033, meropenem- curcumin P-value = 0/006, amikacin- curcumin P-value = 0/003). Also, with the increase of the amount of antibiotic and this ratio reached 25:75 (respectively curcumin: antibiotic), the mean and standard deviation of the diameter of the non-growth halo against Pseudomonas aeruginosa increased more strongly. The        non- growth halo of antibiotics rifampin, meropenem, and amikacin alone were 8/88 ± 0.0 mm, 31/11 ± 0/1 mm,       32/29 ± 0/0 mm, respectively, and in combination with curcumin were 24/5 ± 2/8 mm, 47/6 ± 0/7 mm, 49/8 ± 1/4 mm, respectively (all P-values less than 0/05).

Curcumin has a synergistic effect on the activity of rifampin, meropenem and amikacin antibiotics, and with increasing curcumin ratio, its effectiveness increases.

Escherichia coli, as a member of the Enterobacteriaceae family, belong to the group of facultative anaerobic gram-negative bacilli, and could be an important cause of hospital infections in intensive care units. Due to the widespread use of antibiotics, antibiotic resistance is one of the biggest causes of antibiotic treatment failure. Lactobacillus lactic acid bacteria (LAB) are one of the most important strains of probiotics, which have also been considered for their anti- cancer properties since the antimicrobial effects of some probiotics have been determined. This research aims to investigate the effect of Lactobacillus rhamnosus probiotic on blaCMY beta- lactamase gene expression in Escherichia coli clinical isolates.

In this experimental study, 60 Escherichia coli isolates were collected from hospitals in Mashhad and Neishabur and confirmed by microbiological and biochemical tests. The test to determine the drug sensitivity of the samples to antibiotics was done by the disc diffusion method. Then the resistant isolates were isolated and after re-cultivation, they were treated with probiotic extract. After that, their minimum growth inhibitory concentration (MIC) was compared to these antibiotics by conducting serial dilution method according to CLSI standards. Then, using real- time PCR, the expression of blaCMY gene in control and treatment samples was investigated and compared with each other. Statistical analysis was done with SPSS (independent t-test).

The findings showed that the gene expression in samples treated with Lactobacillus rhamnosus probiotic extract was significantly reduced compared to the control samples (P < 0.001). The mean and standard deviation of the treatment group and control group are 0.35 ± 0.1 and 0.1 ± 1 respectively.

Lactobacillus rhamnosus probiotic extract exerted bactericidal effects through its binding ability, competitive power, and the power to inhibit uropathogens.

Osteosarcoma (OS) is one of the most common bone cancers that constantly affect children, teenagers, and young adults. The limitation of the effectiveness of current treatments of this disease has been confirmed. Rehabilitation exercises are one of the methods that are said to have a good effect, but there are few studies about this. Osteosarcoma is a malignant bone tumor that arises from primary bone - forming cells, and the production of malignant bone material is its prominent histological sign. The purpose of this study was to investigate the effects of combining rehabilitation exercises with vitamin D consumption on the serum level of osteocalcin, insulin resistance, and the function of pancreatic beta cells in patients with osteosarcoma cancer after bone marrow stem cell transplantation.

This study was experimental. Forty female patients with osteosarcoma cancer with a body mass index above 30 kg/m2, age 24.9 ± 4.03 years, height 163.8 ± 3.6 cm, and weight 82.1 ± 4.5 kg were the research subjects. The subjects were randomly divided into four groups (control) (patient - exercise), (patient - exercise - placebo) and (patient-exercise - vitamin D). The training protocol included ten weeks of Pilate’s sports activity, three sessions per week (30 sessions). The weekly supplement group consumed 500 IU of vitamin D for 10 weeks. Data were analyzed using dependent t-test and covariance analysis of variance (P = 0.05).

Rehabilitation exercises combined with vitamin D consumption caused a significant increase in osteocalcin     in control groups (23.7 ± 3.5), patient - exercise (26 ± 14.4), patient - exercise - placebo (26.6 ± 14.1). And patient - exercise - vitamin D (26.4 ± 23.1) and a significant decrease in blood glucose of control groups (82.1 ± 29.9), patient - exercise (72 ± 0.49), patient - exercise - placebo (71 ± 1.32) and patient - exercise - vitamin D (71.5 ± 22.8) of people with osteosarcoma cancer after bone marrow stem cell transplantation. Covariance analysis of the findings of this research showed that rehabilitation exercises along with vitamin D intake caused a non-significant increase in insulin sensitivity in the control groups (36.3 ± 63.4), patient- exercise (37.2 ± 11.2), patient - exercise - placebo(37 ± 2.22) and patient - exercise - vitamin D (37 ± 12.1) and pancreatic beta cell function of control groups (1.5 ± 1.1), patient - exercise (1.1 ± 1.9), patient - exercise - placebo (1.6 ± 1.77) and patient - exercise - vitamin D (1.9 ± 3.2). Also, ten sessions of rehabilitation exercises with vitamin D consumption caused a non-significant decrease in insulin resistance in the control groups (1.2 ± 56.7), patient-exercise (1.7 ± 45.1), Patient-exercise-placebo (12.2 ± 1.3) and patient - exercise - vitamin D (33.3 ± 1.1).

The findings of this research showed that ten weeks of rehabilitation exercises combined with vitamin D intake caused a significant increase in osteocalcin and insulin and a significant decrease in blood glucose in patients with osteosarcoma cancer.

The emergence of drug resistance and treatment- renitent Mycobacterium tuberculosis has made controlling the disease a challenge. World Health Organization (WHO) estimates that approximately 500,000 new cases of tuberculosis occur annually. Considering that mechanisms involved in drug resistance are yet to be elucidated and results of the studies are not consistent, we decided to investigate the correlation between mutations in thyA gene and resistance to para- aminosalicylic acid (PAS).

In this descriptive cross- sectional study, a total of 255 positive MTB specimens were isolated during a three- year period using standard microscopic and culture methods from which 68 Multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis samples were selected through drug susceptibility testing. Then, to determine potential mutations in thyA gene, the fragment was amplified using conventional PCR and products were sequenced. Afterward, mutations which have been induced amino acid substitutions were evaluated with various protein prediction tools. Also, the correlation between mutations and drug resistance was statistically determined using chi-square test.

From 255 clinical TB samples, 68 (26.7%, CI 21.3%) MDR / or XDR-TB strains were isolated. In total, 13 (19.1%) were PAS- resistant and 5 (38.4%) of them had different nucleotide mutations in thyA gene. All of the mutations were statistically correlated with drug resistance. Moreover, the results of bioinformatics showed that identified mutations could lead to the structural and functional disruption of the protein.

According to our results, mutations in thyA gene have appeared to be associated with resistance to PAS. Also, our findings have shed light on the potential of the analysis of short genomic regions and new computational tools in unraveling the molecular mechanisms of drug resistance.

Early diagnosis is one of the most important factors in cancer patients’ treatment. Early detection of cancer requires the discovery of sensitive and specific biomarkers. These biomarkers include proteins (i.e., enzymes, receptors, antibodies and peptides), nucleic acids (DNA- based, such as cell-free DNA (cfDNA) or could be RNA-based, such as microRNA or other non-coding RNAs).  In this review, we investigated the role of circulating tumor DNA (ctDNA) biomarker in the diagnosis of cancer.

In order to find articles related to the purpose of the research, keywords ctDNA and cancer and diagnosis were searched in Google Scholar, PubMed and Web of Science databases. After reviewing 312 found articles, the articles without exact subject and purpose relevance were excluded from the study. Finally, 174 related articles were included in the study. After linking the findings, the articles were read and the desired content was adapted.

It seems that cfDNA is the result of DNA fragmentation after apoptosis, necrosis, active secretion and damage or death of cells and different tissues and is released into the bloodstream. cfDNA is also used as a biomarker for the diagnosis, recurrence and prognosis of some cancers. Also, ctDNA is a part of cfDNA, which includes small pieces of DNA with a length of less than 200 nucleotides. ctDNA is derived from tumor cells circulating in the bloodstream and lymphatic system. Also, ctDNA may be released directly from cells in the tumor site that are dying due to apoptosis and necrosis, or through active release from healthy tumor cells in the bloodstream and lymphatic system. The amount of ctDNA in different people is different and depends on the type of tumor, its location and for cancerous tumors, the stage of the cancer. Assessing the amount of ctDNA, tracking its mutations and investigating the occurrence of aberrant methylation of ctDNA are important biomarkers in diagnosis, determining prognosis, and the course of treatment for cancer patients. Controlling cancers by measuring dynamic ctDNA in blood, plasma or serum is a new and developing area of research.

It seems that despite the challenges in the clinical application of ctDNAs, they can be used in the early diagnosis of cancer.

The landscape of teaching basic and clinical sciences in medical schools has undergone significant changes in recent decades. Pharmacology, as one of the pivotal medical courses and a key therapeutic tool with unique features such as extensive scope and the necessity of comprehensive learning by students, is considered among the most prominent medical courses. Each medical school must ensure that its graduates have thoroughly learned this course and have acquired the skills to recognize and apply this knowledge in patient treatment effectively. In this regard, we aimed to identify and critique the existing pharmacology teaching methods to propose optimal approaches.

This article utilized conventional teaching methods as keywords, focusing on pharmacology. A review of published articles on medical databases such as PubMed and Science Direct, and finally Google Scholar, along with an exploration of information available on university websites, formed the basis of the study. Teaching methods, along with their advantages and disadvantages, were elucidated.

Among the six conventional teaching methods in medicine, traditional teaching, characterized by didactic lectures, remains the oldest and is widely employed in many universities globally. Subsequent newer methods, such as problem-based learning and case-based learning rooted in clinical experiences, are variably adopted by universities worldwide, each with its unique ranking. Question-based learning and multidisciplinary learning also demonstrate potential, though their implementation is somewhat more complex and requires robust support.

The dynamic landscape of medical pharmacology education reveals a diverse array of teaching methods, each with its distinctive features and noteworthy points. Traditional lecture-based approaches provide a foundational structure, linking theoretical concepts with experiential learning and fostering collaborative models, teamwork, and comprehensive patient care. Meanwhile, technology-enhanced strategies cater to the needs of the digital generation. The efficacy of each method is context-dependent, influenced by geographical location, cultural factors, and the developmental stage of each method.