Archives of Advances in Biosciences
Volume:15 Issue: 1, Winter 2024

MicroRNAs play important roles in regulating gene expression in animals and plants. Many studies used these genetic elements to up- or down-regulate human gene expression. It has been shown that viral miRNAs can target and regulate not only viral genes but also host genes. To date, 48 miRNAs have been identified in Epstein-Barr virus (human gamma-herpesvirus 4). This virus can invade and reside in many human tissues such as epithelial or immune system cells. In this study, we evaluated a novel method of finding miRNAs in the Epstein-Barr virus (EBV).

The entire genome content of human gamma-herpesvirus 4 (EBV) was searched using ab initio prediction algorithm by miRNAFold. Selected sequences screened by homology algorithm of miRBase web server.

Among the identified 12 sequences, two putative miRNAs were selected and their properties were further investigated. The main human gene target of the putative miRNA-1 was BCL11A gene that is related to the B-cell lymphoma, and that of putative miRNA-2 was ZBTB18 gene which is mainly related to the mental retardation.
Previous studies used known EBV miRNAs incorporated in delivering vectors such as lentiviral vectors to target various human genes. The introduced two miRNAs can target genes in some malignancies and other types of disorders.

Because of the high stability of the proposed putative miRNAs, they can be used experimentally to regulate human genes.

Multiple myeloma (MM) is a kind of blood cancer that is caused by the malfunction of plasma cells and their uncontrolled growth, which leads to a decrease in the level of immunity and the formation of bone lesions, especially in the spine, skull, pelvis, and ribs. Common symptoms in MM patients include severe bone pain, kidney problems, anemia, and frequent infections. This study aims to employ appropriate cure models to estimate the cure fraction and prognostic factors affecting overall survival (OS) in MM patients who have undergone transplantation.

This study has analyzed the medical records of 52 patients with multiple myeloma who were admitted to Taleghani Hospital affiliated with Shahid Beheshti University of Medical Sciences in Tehran from January 2010 to August 2016 and were followed up until February 2022. Four cure models were applied to the data and it determined the cure fraction in the Inverse Gaussian model is higher than in other models, so prognostic factors affecting the survival of patients were examined using this model.

The mean age at diagnosis was 53.07 (SD =6.4). The 5-year survival rate for MM patients was 74%, and the long-term survival rate for patients in this study was 54.7%. Using the Inverse Gaussian model, the cure fraction was estimated at 54.4%

This study applies cure models to find prognostic factors based on pre-transplant CBC test on the survival time of MM patients who have been treated with auto-HSCT, so the number of platelets pre-transplantation and the patient's age are effective predictors for overall survival.

Alzheimerʼs disease (AD) has been identified as a progressive memory and cognitive impairment. Some Salvia species are suggested by certain studies for the management of mild to moderate AD. We aimed to evaluate the anti-inflammatory, antioxidant, and anti-apoptotic effects of S. hydrangea on amyloid beta-injected rats.

Rats were pretreated with S. hydrangea for 10 days before amyloid beta (Aβ) injection. Western blotting techniques were used to evaluate protein level of γ-glutamyl cysteine synthetase (γ-GCS), Tumor Necrosis Factor α (TNF-α) and Interleukin-6 (IL-6) in two brain regions: hippocampus and frontal cortex.

Current data show that S. hydrangea extract increased γ-GCS protein levels in amyloid beta injected rats, and pretreatment with S. hydrangea increased it further. Besides, S. hydrangea decreased protein levels of TNF-α and IL-6 in amyloid beta injected rats.

Based on the decreased levels of IL-6, TNF-α, and the increased levels of γ-GCS, it is suggested that the use of S. hydrangea could be protective in neurodegenerative diseases.

Ficus johannis Boiss. is a shrubby species in the family Moraceae, exclusively found in Iran, Afghanistan, and Pakistan. This research studies the total phenolic content, flavonoid concentrations, antioxidant capacity, and antimicrobial activity of this biologically unknown species.

The Leaves and fruits of the plant were gathered from the northern slope of Taftan Mountain in Sistan and Baluchestan, in the summer of 2022. After washing, drying, grinding, and obtaining hydroalcoholic extracts of the fruits and leaves, quantifying the phenolic and flavonoid concentrations was done spectrophotometrically utilizing the Folin-Ciocalteu and aluminum chloride colorimetric techniques, respectively. The anti-radical activity of the organs was assayed via the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) protocol and their antimicrobial effects were assessed using the broth microdilution and streak plate techniques against six bacterial, and three fungal pathogens including Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Staphylococcus epidermidis, Streptococcus pyogenes, Bacillus cereus, Aspergillus fumigatus, Fusarium oxysporum, and Candida albicans.

The phenolic compounds were found to be evenly distributed in both leaf and fruit extracts (around 43 mg GAE/g dry extract) while flavonoids were detected in significantly higher concentrations in the fruit extract (14.62 vs 9.57 mg QrE/g dry extract). The leaf extract was better at scavenging free radicals compared to the fruit extract (IC50 93.79 vs 239.62 μg/ml, respectively), while both extracts showed higher IC50 values than the positive control. The leaf extract showed better inhibitory effects on the tested microorganisms compared to the fruit extract. The leaf extract was effective against all tested bacteria, whereas, among the investigated fungi, only Aspergillus fumigatus was vulnerable to it. Conversely, the fruit extract was able to prevent the growth of all investigated fungal strains, but only two bacterial strains (Streptococcus pyogenes and Klebsiella pneumonia) were affected by it. Moreover, both lea and fruit extracts showed the best antimicrobial activity against Aspergillus fumigatus with MIC values of 128 and 512, repectively.

The Ficus johannis fruits and leaves are great sources of phenolic and flavonoid compounds with moderate anti-radical capacity. Moreover, the fruit extract mainly contains antifungal ingredients while the leaf extract chiefly includes antibacterial agents.

Multiple sclerosis (MS) is a complex autoimmune disorder of the central nervous system that affects millions of individuals worldwide. While the etiology of MS remains multifactorial and incompletely understood, emerging evidence suggests that various environmental and lifestyle factors may influence its onset and progression. Among these factors, breastfeeding has gained attention as a potential protective mechanism against the development of MS. However, it is unclear whether breastfeeding, colostrum feeding, and formula or cow milk intake during infancy have any relationship with the development of MS, which type of MS would be influenced further, and if breastfeeding has any effect on the age of MS onset.

100 MS patients and 100 healthy controls took part in this study. Male to female ratio was similar in both groups. Demographic characteristics and history of breastfeeding were collected via a questionnaire.

The mean duration of breastfeeding was considerably lower in some MS patients who had onset of the disease before or at the age of 30 compared to those with onset after 30 years (15.2 + 10.2 versus 19.5 + 11.0 months, P = 0.09). Breastfeeding with a duration of more than 11 months was more frequent in the latter group (83% versus 60%, P = 0.044). Patients with age-onset before or at 30 also revealed a higher rate of feeding with formula or cow milk (56.5% versus 33% and P = 0.063). More frequent feeding with formula or cow milk among MS patients compared to healthy controls (51% versus 31%, P=0.006) was observed.

Formula or cow milk consumption during infancy may be a considerable risk factor for developing MS besides other etiologic factors.

Drugs are among the opioid-like compounds that lead to the development of emotional behaviors in humans and animals. One of the emotional behaviors is stress behavior caused by fear, which can be caused by opioid and quasi-opioid compounds. In this study, the effect of intraventricular injection of brain (I.C.V) agonist (morphine sulfate) and hair receptor antagonist (naloxone) on fear behavior in adult male Wistar rats was investigated.

In this study, pure harmalin was used as a hallucinogenic drug that causes hallucinations and fear in animals as a positive control and saline as a sham was used for comparative studies with groups treated with morphine sulfate and naloxone. In this study, stereotax machine was used for cannulation and injection of I.C.V and Elevated plus-maze machine was used for behavioral testing.

The values used to treat the experimental groups for morphine sulfate (0.5, 1, 2.5, 5, 7μg/rat) and naloxone (0.5, 1, 2μg/rat) were selected. The results of intraventricular injection of (1, 2.5, 5μg/rat) morphine in the brains of rats in the experimental group showed a significant difference in the occurrence of fear behavior compared to the positive control group with P <0.05.
While injection of values (0.5, 7μg/rat) did not show a significant difference with p <0.05 compared to the positive control group. Also, the results of intraventricular injection (I.C.V) of naloxone (1μg/rat) showed a significant difference with p <0.05 in the occurrence of fear behavior in comparison with the positive control group. While injection of values (0.5, 2.5μg/rat) did not show a significant difference with P <0.05 compared to the positive control group. In this study, I.C.V (50 μg / rat) injection of pure harmalin, which is considered as a positive control group, shows the percentage of entry into the open arm and also the percentage of retention time in the open arm.

In conclusion, none of the data used in the present study in the area has a uniform performance and this diversity can be considered as a result of various mechanisms that require more detailed studies.

The Nigella sativa plant, commonly known as black seed, contains a significant compound known as thymoquinone, which exhibits remarkable therapeutic properties. This study aimed to assess the potential therapeutic effects of thymoquinone on the adverse effects of chlorpyrifos toxicity, considering the importance of reproductive capacity and the detrimental impacts of agricultural toxins.

Various parameters were assessed in 36 NRMI male mice including testosterone and luteinizing hormone (LH) hormone secretion, sperm count and motility, as well as an antioxidant activity measured by TAC (Total Antioxidant Capacity), MDA (malondialdehyde), and SOD (Superoxide Dismutase). Both thymoquinone and chlorpyrifos were injected intraperitoneally for 14 days.

In tests related to sperms, chlorpyrifos caused a severe decrease in sperm motility and number (p<0.001). The administration of chlorpyrifos poison caused a significant decrease in the secretion of testosterone and LH hormones (p<0.05). However, these adverse effects were partially reduced by thymoquinone injection together with chlorpyrifos, especially at a dose of 10 mg/kg. Based on the results of TAC, MDA and SOD antioxidant assays, chlorpyrifos poison caused a significant decrease in antioxidant capacity (p<0.001). In contrast, injection of thymoquinone with a dose of 10 mg/kg caused a significant improvement in the increase of antioxidant capacity in the testicular tissue (p<0.05).

According to the observed results and therapeutic effects, a dosage of 10 mg/kg thymoquinone is recommended for reduce oxidative stress-induced injury and toxin-mediated toxicity and enhance sexual traits. Overall, thymoquinone shows potential as a therapeutic agent, and further research could explore its applications in mitigating oxidative stress-related damage and improving sexual function.

Context: 

Dengue fever has been reported in 129 countries worldwide, including 100 countries in the Mediterranean region, South America, and Southeast Asia. It results in approximately 40,000 deaths each year, and there have been significant outbreaks of dengue fever in these areas in recent years. Approximately 50% of the global population is presently susceptible to acquiring the dengue virus, which is classified as an emerging and re-emerging ailment that is likely to impact several nations in the foreseeable future.

Evidence Acquisition: 

Despite the significant harm inflicted upon human health and the economic conditions of countries in recent years, dengue continues to be classified as a neglected disease, without the requisite attention and concerted efforts by countries to effectively manage it. Any actions taken in this domain are inherently constrained. Consequently, due to the significance of dengue fever, this study aims to comprehensively examine this matter.

The disease used to be effectively managed in regions like the countries of the American continent and Singapore, but it has made a resurgence. Between 2008 and 2010, the number of cases in the regions of America, Southeast Asia, and the Western Pacific rose from 0.2 million to 2.2 million. These reports exclusively consist of officially documented sick cases. Multiple outbreaks have been documented in Asia, encompassing countries such as China, Pakistan, Taiwan, and Malaysia, as well as in South America, including Brazil and Mexico. Dengue fever cases have been documented in several Middle Eastern nations, including Yemen, Saudi Arabia, and southern Iran. Local transmission of the disease has begun in Europe, with France and Croatia reporting cases of local transmission. Annually, a minimum of 500,000 individuals experience serious illnesses requiring hospitalization. Approximately 2.5% of individuals who contract the condition die from it. Every year, numerous severe cases of dengue fever are documented, resulting in at least 20,000 deaths.

Dengue fever is a complex systemic disease. Assessing the complete range of the disease burden of dengue fever will be crucial to properly comprehend the serious medical and economic repercussions it has on patients and the general public.

Monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) have changed the face of cancer treatment methods drastically. Herein, I attempted to conjugate a podoplanin (PDPN)-single-chain fragment variable (scFv) to granzyme B (GrB) to design an antibody conjugate (named LpMab-2-(G4S)3-GrB) using in-silico techniques.

The 3D models of the PDPN -specific scFv (LpMab-2), LpMab-2-(G4S)3-GrB, and PDPN were predicted by GalaxyWEB, assessed through Ramachandran plot analysis, and refined by 3Drefine. The physicochemical properties, solubility value, and Tm of LpMab-2-(G4S)3-GrB were estimated/predicted and compared with LpMab-2 and GrB. Finally, the binding capacity of LpMab-2-(G4S)3-GrB to PDPN was compared with that of LpMab-2 through docking and affinity prediction alongside identifying the residues that participate in the binding through 2D interaction plots using the LigPlot+ software.

The 3D models were predicted to be of high quality and refined successfully. The solubility and Tm of LpMab-2 were predicted to decrease and increase following its conjugation with GrB, respectively, whereas its estimated half-life was not affected. The docking results indicated that LpMab-2-(G4S)3-GrB targets PDPN in the same orientation as that of LpMab-2 and with the exact same residues as indicated by their 2D plots. Moreover, the affinity of LpMab-2-(G4S)3-GrB to PDPN was predicted to be similar to that of the single scFv.

The conjugation of LpMab-2 to GrB does not affect its binding capacity or characteristics in a major negative fashion. In-silico techniques could be utilized for antibody engineering, and future studies could focus on the assessment of LpMab-2-(G4S)3-GrB in vitro and in vivo. 

Context: The investigation of obsessive-compulsive disorder (OCD) is paramount in comprehending the fundamental causes, symptoms, and potential therapeutic approaches for this incapacitating psychological condition. OCD is characterized by intrusive thoughts or obsessions, as well as repetitive behaviors or compulsions, which hinder daily functioning and may impact sleep patterns. Understanding the underlying mechanisms of OCD can aid healthcare professionals in devising more efficacious treatment modalities and interventions for individuals afflicted by this disorder. Research on this mental illness can also help diminish the stigma surrounding mental health disorders and promote awareness regarding the importance of seeking assistance for those grappling with OCD. Additionally, research on OCD is imperative for advancing our understanding of the brain and mental health in a broader sense. Such investigations could yield groundbreaking discoveries that might ultimately enhance the overall quality of life for individuals suffering from OCD and other related mental health issues. Evidence Acquisition: Treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) or cognitive-behavioral therapy (CBT), alone or in a combined approach, are considered to be the most effective methods for treating OCD. In addition, Neurofeedback has also represented promise as a treatment for OCD. The difficulties that people with OCD encounter on a daily basis, including the effects on their relationships, career, and emotional well-being, will be covered in this article.

Therefore, in this review, we intend to discuss most popular and efficient OCD treatments, including CBT, SSRIs, and neurofeedback. The pros and cons of these treatments will be covered.

Despite extensive studies, the use of neuroimaging and electroencephalogram (EEG) comparisons in understanding and treating OCD is not well investigated. EEG studies have yielded promising results in identifying neural patterns associated with OCD and determining the efficacy of different treatment approaches.

Anemia is defined as a reduced hemoglobin content leading to minimized oxygen carrying capacity of the cell. Children are commonly affected by anemia which causes impaired development and cognitive defects in them. Among all the causes, iron deficiency is one of the most important contributing factors to the development of anemia. The prevalence of anemia varies in different regions. This study aims to find the prevalence of anemia among children in an urban population of Kerala.

This was a retrospective observational study involving 192 children. The children were diagnosed as anemic if hemoglobin value was less than 11g/dl for those younger than 5 years and less than 11.4g/dl in those aged 5-11 years. The children were further diagnosed with mild, moderate or severe anemia based on their hemoglobin levels. Data were retrieved from the hematology reports and tabulated in Microsoft Excel. Analyses were done using SPSS software version 16.0.

This study showed the prevalence of anemia to be 54.7%. The majority of anemic children (48.6% ) were mildly anemic while 34.3% were moderately anemic, with 17.1% being severely anemic.

In spite of active policy implementation for elimination of anemia, the prevalence of anemia continues to be high indicating the need for active intervention with early detection and treatment of anemia as a routine procedure.

Stereological methods to measure structural changes play an important role for diagnosing and evaluating the healing process of diseases in organs. Zoledronate, used to treat bone diseases, causes osteonecrosis of the jaw following mechanical injuries and is a challenge in clinical settings. This experiment aimed to investigate histopathological changes in subcomponents of mandibular bone trabeculae after mechanical trauma in zoledronate-induced rats by using stereological methods.

Fifty female rats (220-270g) were randomly assigned to experimental and control groups. 25 rats in the experimental group were injected 0.06 mg/kg zoledronic acid (ZA) intraperitoneally, and 25 animals in the control group were injected saline. Injection was performed once a week for 8 weeks, and then dental extraction was done for each animal. Four weeks after extraction, the rats were euthanized and the right hemimandibles were removed, decalcified, cut into serial sections at 5 microns, stained with hematoxylin-eosin, and subjected to stereological analyses. Data were analyzed by using SPSS version 26.

The volume of bone matrix and empty lacunae was significantly higher in experimental rats than that in controls four weeks after extraction (P < 0.05). Reduction of the volume of osteocytes, osteoblasts, osteoclasts, and Howship’s lacunae in experimental group was observed when compared with the controls (P < 0.05).

The stereological methods in the present study provided a standardized and reproducible methodology for quantitative analysis of histopathological changes and can be used as a basis for future studies investigating preventive or therapeutic strategies for Medication-Related Osteonecrosis of the Jaw (MRONJ) that are evidence-based and associated with accurate and valid data.

Aflatoxins are toxic metabolites produced by certain fungi, primarily Aspergillus species, that contaminate various food and feed crops. Alkaloids, a diverse group of naturally occurring compounds found in plants, animals, and microorganisms, have been investigated as potential inhibitors of polyketide synthase in aflatoxin biosynthesis. The purpose of this study is to investigate the inhibitory potential of a few alkaloid compounds against aflatoxin biosynthesis polyketide synthase.

The 2D structures of 10 alkaloid compounds, used as ligands, were obtained from PubChem database and optimized using the MM2 Job command in Chem3D Pro 12.0.2.1076 software. The ligands were assessed as inhibitors against the active site of the aflatoxin biosynthesis polyketide synthase protein using AutodackVina software. The results were analyzed using Discovery Studio v16.1.0 software.

Among the compounds studied, atropine, hyoscyamine, morphine, and strychnine exhibited the highest binding affinities with values of -11.9, -10.8, -11.5, and -11.1 kcal/mol, respectively, for the 3HRR (aflatoxin biosynthesis polyketide synthase) protein. Additionally, neurocaine and morphine demonstrated notable binding affinities of -11.6 and -12.9 kcal/mol, respectively, for the 3HRQ (Biosynthetic) protein. Notably, morphine displayed the strongest inhibitory activity against both proteins, with key amino acids aspartic acid (1395), alanine (1397), and valine (1394) for 3hrr protein, and glycine (1340), asparagine (1502), and arginine (1343) for 3hrq protein.

Aflatoxins represent serious health risks due to their potent carcinogenic and hepatotoxic properties. The findings of this study revealed the inhibitory potential of morphine. Consequently, combinations of alkaloids with a central structure similar to morphine may be promising candidates as anti-aflatoxin agents, warranting further investigation and development for drug research.

Context: 

Diamond-Blackfan anemia (DBA) is a rare autosomal recessive disorder characterized by erythroblastopenia and pure red cell aplasia. The condition typically results from an abnormality in a ribosomal protein gene.

Cases of cytopenia have been linked to ADA2 deficiency caused by CECR1 mutations. In the current case study, a child presented with severe anemia requiring multiple RBC transfusions due to the condition going undiagnosed. After 8 years, the patient developed elevated ferritin levels, severe neutropenia, and a serious infection that complicated the clinical picture. Molecular analysis revealed homozygous variants (c.140G>T p.Gly47Val) in the ADA2 gene inherited from heterozygous parents.

This case represents the first documented instance in Iran, highlighting the importance of screening for congenital defects in seemingly healthy couples, especially emphasizing the need for prenatal diagnosis (PND) using molecular methods and genetic sequencing.

The present study aims to evaluate the possible amelioration of the toxic effect of Pb2+ on the liver and kidney organs of zebrafish (Danio rerio) by the probiotic strain Lactobacillus fermentum as a dietary supplement.

Zebrafish that had beedn treated with probiotics for 60 days were exposed to 0-1500 μg/L Pb2+ for 72h. The LC50 for the control group was determined, and biometric, histological, and antioxidant biomarkers were assessed. This included lipid peroxidation, SOD (superoxide dismutase) activity, reactive oxygen species (ROS) levels, and inflammatory response, focusing on interleukin-8 (IL-8) and interferon-gamma (IFN-γ) gene expression.

Based on morphological analysis, the probiotic-enriched diet had no significant effect on the weight and length of zebrafish as biometric parameters. However, it reduced tissue heavy metal accumulation and mortality by 83% at 1500 μg/L Pb2+ after 72 hours of T2 treatment. Tissue damage, including hepatocyte necrosis, renal and tubular degeneration, decreased significantly in treated groups. Oxidative stress analysis revealed that probiotic treatment alleviated free radical production, SOD activity, and malondialdehyde (MDA) levels in zebrafish, allowing them to tolerate more than 300 μg/L Pb2+. In addition, probiotic-treated zebrafish showed a significant recovery in SOD2, IL-8, and IFN-γ mRNA expression, indicating an improved immune system.

In conclusion, a diet enriched with Lactobacillus fermentum reduced the oxidative stress and improved the resistance of zebrafish to the sub-lethal dose of Pb2+. Overall, Lactobacillus fermentum shows potential as a dietary supplement for aquaculture in Pb2+-contaminated areas.

The management of advanced-stage solid tumors remains a formidable challenge in oncology, often necessitating a combination of treatment modalities with limited efficacy. Nucleic acid-based drugs have emerged as promising therapeutic options, offering novel approaches to combat treatment-resistant tumors. This editorial review briefly analyzes viral and non-viral nucleic acid-based treatments for solid tumors, including their development, clinical activity, mechanisms of action, and prospects. Viral vectors, such as adenoviruses and lentiviruses, enable the delivery of therapeutic genes directly into tumor cells or the modulation of the tumor microenvironment, resulting in regulatory approvals for several gene therapies. Non-viral delivery systems, including lipid nanoparticles and polymer-based carriers, offer alternative strategies for transporting therapeutic nucleic acids into tumor cells, with precise drug release and targeting control.

The literature review is based on searches of the PubMed database, Web of Science, Scopus, and Google Scholar using specific keywords. The article is based on manuscripts published between 2021 and 2024.

The mechanistic actions of nucleic acid-based drugs are diverse, encompassing direct tumor cell killing, modulation of the immune response, and inhibition of oncogenic pathways. Importantly, these therapeutic approaches demonstrate a favorable safety profile compared to traditional chemotherapy agents, minimizing off-target effects and reducing adverse events. The tumor microenvironment significantly influences the effectiveness of nucleic acid-based therapies, requiring strategies to improve drug delivery and overcome resistance mechanisms. Ongoing clinical trials, preclinical studies, and advancements in manufacturing and stability technologies are expected to drive the next generation of nucleic acid agents, ensuring widespread accessibility and clinical utility.

Nucleic acid-based drugs represent a transformative approach to cancer therapy, potentially revolutionizing treatment outcomes and ushering in an era of precision medicine in oncology.