Newly discovered functions of miRNAs in neuropathic pain: Transitioning from recent discoveries to innovative underlying mechanisms.

Neuropathic pain is a widespread clinical issue caused by somatosensory nervous system damage, affecting numerous individuals. It poses considerable economic and public health challenges, and managing it can be challenging due to unclear underlying mechanisms. Nevertheless, emerging evidence suggests that neurogenic inflammation and neuroinflammation play a role in developing pain patterns. Emerging evidence suggests that neurogenic inflammation and neuroinflammation play significant roles in developing neuropathic pain within the nervous system. Increased/decreased miRNA expression patterns could affect the progression of neuropathic and inflammatory pain by controlling nerve regeneration, neuroinflammation, and the expression of abnormal ion channels. However, our limited knowledge of miRNA targets hinders a complete grasp of miRNA's functions. Meanwhile, exploring exosomal miRNA, a recently uncovered role, has significantly advanced our comprehension of neuropathic pain's pathophysiology in recent times. In this review, we present a comprehensive overview of the latest miRNA studies and explore the possible ways miRNAs might play a role in the development of neuropathic pain.

High prevalence and expression of antiseptic resistance genes among infectious t037/ST239 methicillin-resistant Staphylococcus aureus (MRSA) strains in North Khorasan Province, Iran.

Objectives: Staphylococcus aureus is an important infectious agent and the majority of methicillin-resistant S. aureus (MRSA) infections are of nosocomial origin. To define the level and distribution of antiseptic resistance among infectious S. aureus strains we studied MRSA and methicillin-susceptible S. aureus (MSSA) isolates collected from different infection sites in an assortment of patients. Materials and Methods: S. aureus isolates were investigated for in vitro susceptibility to antiseptic agents and detection of qacA/B, smr, vanA, and mecA genes. Results: Among the S. aureus isolates we studied, 25 and 41 were MRSA and MSSA, respectively. The mean of minimum inhibitory concentrations (MICs) for benzethonium chloride (BTC) among MRSA was statistically significantly higher than for MSSA (26 µg/ml versus 11.7 µg/ml, P=0.003) while there was no significant difference between MRSA and MSSA for benzalkonium chloride (BKC) and chlorhexidine digluconate (CHG). The qacA/B genes were carried in 68% of the MRSA and 58.2% of MSSA (P=0.601), while smr was carried in 39% of MRSA and 29.3% of MSSA strains (P=1.000). In 15 out of 25 cases, MRSA ST239 with spa types t037, t030, and t7688 was isolated from the infection site with 86.6% of them carrying a resistance gene (qacA/B or qacA/B + smr). Conclusion: The frequent presence of antiseptic resistance genes and a consequently elevated MIC against antiseptics among ST239 MRSA emphasizes the importance of mandatorily monitoring MRSA for effective infection control.

High-level seroprevalence against Leptospira interrogans serovars among wild foxes, jackals and stray dogs in the North Khorasan Province, Iran.

BACKGROUND: Leptospirosis is an important, neglected zoonotic disease that affects people and animals in humid (sub)tropical regions. Wild canines carry the pathogen and may contaminate natural resources which may then act as a source of human infection. OBJECTIVES: The study was designed to understand the seroprevalence of leptospirosis among domestic and wild canines in Bojnurd County, Northeast Iran. METHODS: A total of 77 serum samples, comprising 29 sera from asymptomatic wild canines [foxes (n = 25) and jackals (n = 4)] and 48 sera from asymptomatic stray dogs, was investigated. Serovars were identified and antibody titres were measured by standard microscopic agglutination test (MAT) using serial serum dilutions. RESULTS: Among all serum samples, 44.1% reacted positively to a Leptospira interrogans serovars. The average percentage of positive reactions was higher in stray dogs than in wild canines although this did not reach statistical significance (55.2% and 37.5%, p = 0.159). Positive reactions with L. i. Pomona, L. i. Australis and L. i. Tarasovi was detected only among jackals and foxes. Among the stray dogs, the highest number of positive sera were for L. i. Grippotyphosa (61.1%) and L. i. Canicola (50%). The highest titre detected was for L. i. canicola (1:1600) in two stray dogs and against L. i. Icterohaemorrhagiae and L. i. Pomona (1:800) in a single jackal. CONCLUSIONS: The study revealed that leptospirosis is endemic among various canine species in the North Khorasan Province of Iran. Detailed monitoring of canines is necessary for better understanding the epidemiology of infection in our and other Iranian regions.

Survival of the hospitalized patients with COVID-19 receiving atorvastatin: A randomized clinical trial.

As statins decrease the progression of sepsis and its related mortality, this study aimed to evaluate the effect of atorvastatin on survival and symptom improvement in hospitalized patients with COVID-19. This randomized controlled trial was performed on 156 hospitalized patients with COVID-19 in Bojnourd city in 2021. Patients were randomly divided into comparison (standard therapy: hydroxychloroquine + Kaletra®) and intervention groups (atorvastatin 20 mg, SD, plus standard therapy). The main outcomes were the rate of symptom improvement, duration of hospitalization, need for intubation, and mortality rate. In this study, seven patients died, two patients (2.6%) in the comparison group and five (6.6%) in the intervention group. The mean hospitalization days (p = 0.001), the pulse rate (p = 0.004), and the frequency of hospitalization in the ICU ward (18.4% vs. 1.3%) were longer and greater in the intervention group. The remission probability in the comparison group was greater (p = 0.0001). The median hospitalization days in the intervention group was longer (p < 0.001) and remission in the comparison group occurred 1.71 times sooner (hazard ratio = 1.70, 95% confidence interval = 1.22-2.38, p = 0.002). Totally, adding atorvastatin to the standard regime in this study increased hospitalization days and imposed negative effects on symptom improvement in hospitalized patients with COVID-19.

Evaluation of the relationship between serum levels of zinc, vitamin B12, vitamin D, and clinical outcomes in patients with COVID-19.

Due to the known anti-inflammatory and antiviral effects of zinc, 25(OH)D, and vitamin B12, in this study, we explored the association between serum levels of these micronutrients in coronavirus disease 2019 (COVID-19) patients at the time of admission and the clinical outcomes. This study was carried out on 293 patients with COVID-19, who were hospitalized at Imam Hassan hospital (Bojnourd, Iran). We collected demographic data, clinical characteristics, values of serum biochemical parameters in the first week of admission, and clinical outcomes from electronic medical records. We also measured serum levels of zinc, 25(OH)D, and vitamin B12 within 3 days of admission. Of the 293 hospitalized, the median age was 53 years, and 147 (50.17%) were female. Thirty-seven patients (12.62%) were admitted to the intensive care unit (ICU), and forty-two (14.32%) died. We found that the serum levels of zinc, vitamin B12, and 25(OH)D were lower in patients who died than those who were admitted to ICU or non-ICU and survived; however, these differences were not statistically significant for vitamin B12 and 25(OH)D (p > 0.05). The serum concentrations of zinc, vitamin B12, and 25(OH)D at the time of admission did not affect the length of hospital stay in patients with COVID-19. In general, it seems that serum levels of 25(OH)D, vitamin B12, and especially zinc at the time of admission can affect clinical outcomes in COVID-19 patients.

Higher detection of JC polyomavirus in colorectal cancerous tissue after pretreatment with topoisomerase I enzyme; colorectal tissue serves as a JCPyV persistence site.

BACKGROUND: The JC polyomavirus has been blamed to contribute in colorectal cancer (CRC), however, the topic is still controversial. Varying detection rate of JCPyV genome has been reported mainly due to technical reasons. Here, we provide summative data on the topic, with emphasize on technical issues. METHODS: Formalin-fixed paraffin-embedded tissue samples from 50 patients with CRC, consisting of tumoral and non-cancerous marginal tissue (totally 100 samples) were included in the study. After DNA extraction, specific JCPyV T-Ag sequences were targeted using Real-time PCR. To unwind the supercoiled JCPyV genome, pretreatment with topoisomerase I, was applied. Immunohistochemical (IHC) staining was performed using an anti-T-Ag monoclonal antibody. RESULTS: In the first attempts, no samples were found to be positive in Real-time PCR assays. However, JCPyV sequences were found in 60% of CRC tissues and 38% of non-cancerous colorectal mucosa after application of pre-treatment step with topoisomerase I enzyme (P = 0.028). T-Ag protein was found in the nuclear compartment of the stained cells in IHC assays. CONCLUSIONS: The presence of JCPyV in CRC tissues, as well as T-Ag localization in the nucleolus, where its oncogenic effect takes place, may provide supporting evidence for JCPyV involvement in CRC development. The study highlights the importance of using topoisomerase I to enhance JCPyV genome detection. Also, colorectal tissue is one of the permissive human tissue for JC resistance after preliminary infection.

Silencing SALL-4 Gene by Transfecting Small Interfering RNA with Targeted Aminoglycoside-Carboxyalkyl Polyethylenimine Nano-Polyplexes Reduced Migration of MCF-7 Breast Cancer Cells.

BACKGROUND: The application of non-viral systems for delivering genes to cells is becoming a very interesting issue, especially in the treatment of neoplasms such as Breast Cancer (BC). Polymer-based non-viral systems are safe and feasible gene carriers to be used in targeted cancer therapy. SALL4 gene encodes a transcription factor and is overexpressed in some cancers. METHODS: In this study, carboxyalkylated-PEI25 (25 kDa) was used to deliver plasmids expressing SALL4-siRNA into MCF-7 cells. DLS and AFM were applied to determine the size of nanoparticles. The MTT method was used to assess cytotoxicity, and the efficiency of transfection was confirmed both qualitatively and quantitatively. Finally, the effect of silencing SALL4 was investigated on the migration of MCF7 cells using the scratch test. RESULTS: The results showed that transferring the SALL4-siRNA using PEI25G10C50 reduced the expression of the corresponding transcription factor by 14 folds which attenuated the migration of MCF-7 cells by 58%. CONCLUSION: In conclusion, PEI25G10C50 can serve as an effective gene delivery system for treating BC by targeting SALL-4.

Seroprevalence of Leptospira infection in occupational risk groups in North Khorasan province, Iran.

Leptospirosis is an important zoonotic bacterial disease caused by Leptospira spp. Earlier studies from North Khorasan province (Iran) reported the presence of Leptospira in wild canines and rodents. To date, there is no data on the seroprevalence of leptospirosis among humans in this province. This study was performed to determine the prevalence of human leptospiral infection among people with different occupations. The study was conducted in urban and rural areas of the province. Among the serum samples collected from 278 subjects, 3 (1.1%) showed positive reaction with titer of 1:100 by the microscopic agglutination test (MAT). Positive reactions were detected against Leptospira interrogans Canicola and L. interrogans icterohemorrhagic and all these samples were from livestock farmers (n = 3/106, 2.7%). The current study revealed that, though Leptospira infection is low in North Khorasan province, regular monitoring of the livestock and the farmers are important.

High prevalence of SARS-CoV-2 and influenza A virus (H1N1) coinfection in dead patients in Northeastern Iran.

In the last months of 2019, an outbreak of fatal respiratory disease started in Wuhan, China, and quickly spread to other parts of the world. It was named COVID-19, and to date, thousands of cases of infection and death are reported worldwide. This disease is associated with a wide range of symptoms, which makes accurate diagnosis of it difficult. During previous severe acute respiratory syndrome (SARS) pandemic in 2003, researchers found that the patients with fever, cough, or sore throat had a 5% influenza virus-positive rate. This finding made us think that the wide range of symptoms and also relatively high prevalence of death in our patients may be due to the coinfection with other viruses. Thus, we evaluated the coinfection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with other respiratory viruses in dead patients in North Khorasan. We evaluated the presence of influenza A/B virus, human metapneumovirus, bocavirus, adenovirus, respiratory syncytial virus (RSV), and parainfluenza viruses in 105 SARS-CoV-2 positive dead patients, using polymerase chain reaction (PCR) and reverse transcription PCR tests. We found coinfection with influenza virus in 22.3%, RSV, and bocavirus in 9.7%, parainfluenza viruses in 3.9%, human metapneumovirus in 2.9%, and finally adenovirus in 1.9% of SARS-CoV-2 positive dead cases. Our findings highlight a high prevalence of coinfection with influenza A virus and the monopoly of coinfection with Human metapneumovirus in children.

Visceral leishmaniasis in an adult case in Northeast of Iran: A case report and literature review.

Leishmaniasis is a rare complication in adult cases even in endemic areas. Here, the first report of visceral leishmaniasis in a young woman in northeast of Iran has been described.

Development of a PCR-RFLP method for detection of D614G mutation in SARS-CoV-2.

In late 2019, an outbreak of respiratory disease named COVID-19 started in the world. To date, thousands of cases of infection are reported worldwide. Most researchers focused on epidemiology and clinical features of COVID-19, and a small part of studies was performed to evaluate the genetic characteristics of this virus. Regarding the high price and low availability of sequencing techniques in developing countries, here we describe a rapid and inexpensive method for the detection of D614G mutation in SARS-CoV-2. Using bioinformatics databases and software, we designed the PCR-RFLP method for D614G mutation detection. We evaluated 144 SARS-CoV-2 positive samples isolated in six months in Northeastern Iran. Our results showed that the prevalent type is S-D in our isolates, and a small number of isolated belongs to the S-G type. Of 144 samples, 127 (88.2%) samples have belonged to type S-D, and 13 (9%) samples typed S-G. The first S-G type was detected on 2020 June 10. We have little information about the prevalence of D614G mutation, and it seems that the reason is the lack of cheap and fast methods. We hope that this method will provide more information on the prevalence and epidemiology of D614G mutations worldwide.

Epidemiology of genital infections caused by Mycoplasma hominis, M. genitalium and Ureaplasma urealyticum in Iran; a systematic review and meta-analysis study (2000-2019).

BACKGROUND: Although many species of mycoplasmas regard as normal flora, but some species causes serious genital disease. In Iran several epidemiological studies have documented the prevalence of Mycoplasma hominis, M. genitalium and Ureaplasma urealyticum in genital disorders. This meta-analysis is going to represent the prevalence of M. hominis, M. genitalium and U. urealyticum among Iranian couples and the correlation between mycoplasmas infection and infertility. METHODS: We search online databases from January 2000 to June 2019. We used following MeSH keywords (Prevalence, M. hominis, M. genitalium, U. urealyticum, male, female, fertility, Infertility, genitourinary tract infection and Iran) with all possible combinations with "OR" and "AND". Finally, forty-four articles from 2670 were chosen for data extraction and analysis by software using STATA version 14.0. RESULTS: This meta-analysis revealed that the prevalence of U. urealyticum was 17.53% in Iran and the prevalence of M. genitalium and M. hominis were 11.33 and 9.68% respectively. The rate of M. genitalium, M. hominis and U. urealyticum infection in women with symptoms of genitourinary tract infection was higher than men with genitourinary tract infection (6.46% vs 5.4, 7.67% vs 5.88 and 21.04% vs 12.13%, respectively). As expected, the prevalence of M. genitalium, U. urealyticum and M. hominis among infertile women (12.73, 19.58 and 10.81%) were higher than fertile women (3%, 10. 85% and 4. 35%). Similarly, the prevalence of M. hominis and U. urealyticum among infertile men (14 and 21.18%) were higher than fertile men (4 and 3%). Based on this analysis, the rate of U. urealyticum was higher than M. genitalium and M. hominis among infertile men and women compared to the fertile group. The prevalence rate of M. genitalium, M. hominis and U. urealyticum in central provinces is higher than other parts of Iran. CONCLUSIONS: This meta-analysis reemphasizes a significant relationship between the infertility rate and U. urealyticum, M. genitalium and M. hominis infections. Our finding help to plan the prevalence map of M. hominis, M. genitalium and U. urealyticum in Iran but further studies are needed to suggest routine screening of the pathogens.

Molecular Detection and Serotyping of Streptococcus pneumoniae in Children with Suspected Meningitis in Northeast Iran.

BACKGROUND: To date, more than 90 Streptococcus pneumoniae (S. pneumoniae) capsular serotypes are known. The prevalence of these serotypes varies according to the geographical area and the regional vaccination program. Due to the lack of regular vaccination programs for S. pneumoniae in developing countries, serotyping of the prevalent isolates is useful in selecting the correct vaccine. The present study aimed to evaluate common serotypes of pneumococcal meningitis in Bojnurd, Iran. METHODS: All cerebrospinal fluid (CFS) samples suspected for bacterial meningitis were analyzed. The samples were collected during 2014-2018 in the Laboratory of Imam Reza Hospital (Bojnurd, Iran). Due to the high rate of false-negative cultures, polymerase chain reaction (PCR) was used for the detection of lytA and psaA genes of S. pneumoniae. In addition, the modified Marimon's PCR method was used for serotyping the bacteria. The data were analyzed using Pearson's Chi-square test. RESULTS: Out of the 901 CSF samples, 106 cases tested positive for S. pneumoniae using the PCR method, while only 92 cases tested positive using the conventional methods. Based on the Marimon's PCR method, serotypes 23F, 19F, 19A, 1, 14, and serogroup 6A/B were the most common types. Serogroups 18C, 15A/F, 15B/C, 9A/V, 7A/F, 11A/D/F, and 22A/F were also detected in isolates. Note that 2.8% of the samples were non-typable (NT). CONCLUSION: The results showed that only 13 serotypes were responsible for all meningitis cases. Pneumococcal capsular vaccine-13 (PCV-13) is the preferred choice against common serotypes of S. pneumoniae in northeast Iran.The abstract was presented in Iran's 19th International Congress of Microbiology, as a poster and published in the congress abstracts book.

Molecular Characterization Of Vancomycin-Resistant Enterococcus faecalis Among Inpatients At Iranian University Hospitals: Clonal Dissemination Of ST6 And ST422.

PURPOSE: Over the past two decades, enterococci have emerged as an important opportunistic pathogen causing life-threatening infections in hospitals. The purpose of the present study was to examine the prevalence of genes encoding virulence factor and molecular characterization of vancomycin-resistant E. faecalis strains isolated from hospitalized patients in Isfahan, the central city of Iran. PATIENTS AND METHODS: A total of 53 vancomycin-resistant E. faecalis isolates (VRE) obtained from clinical samples of hospitalized patients were characterized by phenotypic and genotypic methods, and 25 selected VRE isolates from internal and ICU wards were typed by multilocus sequence typing. RESULTS: The efa was the most prevalent virulence gene (100%) among isolates, followed by gelE (92.45%), asa1 (90.56%), ace (86.79%), esp (75.47%), cylA (39.62%), and hyl (18.86%). More than 80% of the isolates were HLGR. Multilocus sequence typing showed eight different sequence types including ST6, ST422, ST28, ST448, ST531, ST328, ST421, and ST495. STs were grouped into two clonal complex (CC) including CCA (ST6, ST422, ST448, ST531) and CCF (ST28, ST421) and two singletons (ST328, ST495). CONCLUSION: Our data indicated a high prevalence of virulence genes among STs described in this study. In addition, the molecular analysis demonstrated a relatively high genetic diversity among selected VRE strains from the ICU in comparison with the internal ward. Therefore, in order to prevent the colonization of virulent strains in the hospital environment, infection control procedures should be performed.

Detection of Porcine Bocavirus From a Child With Acute Respiratory Tract Infection.

Porcine bocavirus is a recently discovered virus classified within the Bocavirus genus. We present a case of upper respiratory tract infection associated with porcine bocavirus in a 3-year-old child who was in close contact with hogs in northeastern Iran. To the best of our knowledge, this is the first report on the human porcine bocavirus infection.

Association between TPO Asn698Thr and Thr725Pro gene polymorphisms and serum anti-TPO levels in Iranian patients with subclinical hypothyroidism.

OBJECTIVE: Subclinical hypothyroidism (SCH) is defined as high levels of TSH in the presence of normal levels of serum FT4. Since thyroid peroxidase (TPO) plays a key role in thyroid hormone synthesis, variations in the TPO gene can change the enzyme structure and result in the production of anti-TPO antibodies. The aim of this study was to examine the relationship between the Asn698Thr (A2095C) and Thr725Pro (A2173C) polymorphisms of the TPO gene and anti-TPO levels in patients with SCH. DESIGN: In this study, 150 individuals (75 cases and 75 controls), aged 19-75 years, were selected randomly by a clinician. The thyroid function tests included were FT3, FT4, TSH and anti-TPO antibodies using ELISA. The TPO gene polymorphisms were examined by PCR-RFLP. RESULTS: Anti-TPO levels in the experimental group was significantly increased (P=0.020). The A2095C genotype frequency in the experimental and control groups were 37.3% vs 34.7% for the AA healthy genotype, 20% vs 46.7% for AC and 42.7% vs 18.6% for CC, respectively (P=0.001). The A2173C genotype frequency in the experimental and control groups were 22.6% vs 68% for healthy AA, 40% vs 25.3% for AC and 37.4% vs 6.7% for CC, respectively (P <0.001). The increased anti-TPO antibodies were significantly associated with the A2173C polymorphism (P=0.035). The findings showed that the chance (odds ratio) of developing subclinical hypothyroidism in individuals who had C alleles was 1.5 and 5.6-fold higher than in individuals without these alleles in the A2095C and A2173C regions, respectively. CONCLUSIONS: Determination of anti-TPO antibody levels and exon 12 TPO gene polymorphisms in patients with SCH can be helpful for prediction of overt hypothyroidism.

A case of fatal gastrointestinal anthrax in north eastern iran.

Background. Bacillus species are aerobic or facultative anaerobic, gram-positive, or gram-variable spore-forming rods. They are ubiquitous in the environmental sources. Bacillus anthracis may usually cause three forms of anthrax: inhalation, gastrointestinal, and cutaneous. The gastrointestinal (GI) anthrax develops after eating contaminated meat. In this paper we report septic intestinal anthrax. Case Presentation. We report an isolation of Bacillus anthracis from blood culture of patient with intestinal anthrax. Bacillus anthracis was isolated from a blood culture of a 34-year-old man who had a history of severe abdominal pain, bloody diarrhea, nausea, vomiting, fever, sweating, and lethargy within 4 to 5 days after eating the meat of domestic goat. He had evidence of severe infection and septic shock and did not respond to treatments and subsequently expired 9 hours after hospitalization. Conclusion. Gastrointestinal anthrax is characterized by rapid onset, fever, and septicemia. Rapid diagnosis and prompt initiation of antibiotic therapy can help in survival. Most of previous cases of septicemic anthrax were related to injection drug users but, in our case, septicemia occurred after gastrointestinal anthrax.