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Hoda Rahimi,1 Nikoo Mozafari,1 Shahin Bastaninejad,2 Zohreh Tehranchinia,1 Nourullah Aghaebrahimi Samani21Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Otorhinolaryngology Research Center, Tehran University of Medical Sciences, Tehran, IranBackground: Vitiligo is an acquired disorder characterized by depigmented macules and patches that result from a progressive loss of functional melanocytes. During embryogenesis, precursor cells of melanocytes (melanoblasts) migrate not only to the epidermis and hair follicles but also to the leptomeninges, uveal tract of the eye, and inner ear. Thus, it has been proposed that these organs may be involved in vitiligo, as well.Objective: This study was designed to evaluate the frequency and characteristics of hearing loss by means of audiometry and distortion product otoaucostic emission (DPOAE) in patients with vitiligo.Methods: Fifty-three patients with vitiligo and 52 age- and sex-matched healthy subjects were enrolled in this case–control study. After a complete otological examination, comprehensive audiological evaluations including pure tone audiometry (PTA) and DPOAE were performed for all participants and the results were compared between the two groups.Results: Neither PTA nor DPOAE showed significant difference between the two groups in any of the evaluated frequencies (0.75–8 KHz). Furthermore, in patient group, there was no association between PTA/DPOAE and age, gender, duration of the disease, presence of halo nevus, type of vitiligo, extent of involvement, and positive family history of vitiligo.Conclusion: Vitiligo patients have normal hearing status.Keywords: vitiligo, hearing, hypoacusis, OAE, melanocyte

Abstract Background and objectives: Staphylococcus aureus is one of the most important etiological agents of hospital and community acquired infections. The enterotoxins and toxin shock syndrome toxin (TSST-1) are among the most common virulent determinants of this bacterium. They are also well-known for their super-antigenic properties. The incidence of TSST-1 producing strains is also very alarming. The aim of this investigation was to survey the prevalence of TSST-1 gene in the clinical isolates of S. aureus recovered from hospitalized patients in Shohada hospital of Tabriz, Iran. Material and Methods: During one year period, 1454 specimens obtained from hospitalized patients were investigated. After doing Isolation and purification, the isolates were identified by routine bacteriological methodologies.Their antibiotic susceptibility patterns were determined by agar disk diffusion method. Following genomic DNA extraction by boiling method, the presence of TSST-1 gene was analyzed by PCR. Results: A total 100 S. aureus isolates were recovered (6.87%). Antibiogram results indicate that all of the isolates are sensitive to linzolid 83% of them are resistant to meticillin. The prevalence rate of TSST-1 gene in the isolates is 20%. Conclusion: The high prevalence of TSST-1 gene in studied S. aureus strains and their circulation in the community can have a potentially alarming effect on general health of community. Key words: Staphylococcus aureus, TSST-1, Antibiotic resistance, PCR

Deterioration of reinforced concrete structures, namely due to corrosion of reinforcement, in the south of Iran, on the coasts of the Gulf region has become a major problem in recent years. The high cost involved in repairing and strengthening of deteriorated concrete structures in this region makes it essential that the repair materials used are compatible enough to match the residual service life of the structure. This paper presents the engineering and compatibility-related properties of two repair concretes containing silica fume and styrene butadiene rubber latex (SBR) under simulated hot and humid conditions similar to the aggressive environment of the south of Iran. A normal cement-based repair concrete was used as control. Mechanical properties were assessed and the dimensional stability of the repair concretes was also evaluated. The results of this investigation show that the concrete containing silica fume and the polymer-modified concrete are appropriate materials for repair in the severe environmental conditions of the Gulf region. [ABSTRACT FROM AUTHOR]

Background: Burn patients are more likely to get healthcare-associated infections (HAIs). The current study aimed to investigate the characteristics of HAI and mortality risk factors among burn patients admitted to a tertiary center in Iran. Methods: A retrospective study was conducted in 2021 on burn patients who developed HAI after hospitalization in a tertiary center in Ahvaz, Iran. The records of patients admitted and managed between March 2019 and March 2020 were reviewed. Statistical analysis was carried out using IBM SPSS Version 26, with p < 0.05 considered statistically significant. Results: Of the 1,659 admitted patients, 395 (23.8%) developed HAI during the study period. After excluding patients with incomplete medical records and those with fungal or viral infections, 363 patients remained. The majority of these cases occurred in male patients. The most common type of HAI was burn wound infection (56.2%). Patients were mainly affected by Gram-negative bacteria, Pseudomonas aeruginosa (39.7%), while the most common Gram-positive bacteria was Staphylococcus epidermididis (9.6%). The most common antibiotic resistance among P. aeruginosa -infected patients was reported against imipenem, followed by gentamicin and ciprofloxacin; however, the mentioned organism was mainly sensitive to colistin. Gender, age, bloodstream infection (BSI), ventilator-associated infection (VAI), ICU admission, and total burned surface area (TBSA) resulted in 3.585, 1.028, 2.222, 7.469, 5.278-, and 1.031 times higher mortality rates, respectively. Conclusion: Female gender, advanced age, BSI, VAI, and ICU admission are risk factors for HAI. These findings emphasize the need for focused infection prevention and management to improve high-risk burn patient survival., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Nima Mozafari et al.)

Background: Lung cancer's high prevalence and invasiveness make it a major global health concern. The Ki-67 index, which indicates cellular proliferation, is crucial for assessing lung cancer aggressiveness. Radiomics, which extracts quantifiable features from medical images using algorithms, may provide insights into tumor behavior. This systematic review and meta-analysis evaluate the effectiveness of radiomics in predicting Ki-67 status in Non-Small Cell Lung Cancer (NSCLC) using CT scans., Methods and Materials: A comprehensive search was conducted in PubMed/MEDLINE, Embase, Scopus, and Web of Science databases from inception until April 19, 2024. Original studies discussing the performance of CT-based radiomics for predicting Ki-67 status in NSCLC cohorts were included. The quality assessment involved quality assessment of diagnostic accuracy studies (QUADAS-2), radiomics quality score (RQS) and METhodological RadiomICs Score (METRICS). Quantitative meta-analysis, using R, assessed pooled diagnostic odds ratio, sensitivity, and specificity in NSCLC cohorts., Results: We identified 10 studies that met the inclusion criteria, involving 2279 participants, with 9 of these studies included in quantitative meta-analysis. The pooled sensitivity and specificity of radiomics-based models for predicting Ki-67 status in NSCLC were 0.783 (95 % CI: 0.732 - 0.827) and 0.796 (95 % CI: 0.707 - 0.864) in training cohorts, and 0.803 (95 % CI: 0.744 - 0.851) and 0.696 (95 % CI: 0.613 - 0.768) in validation cohorts. It was identified in subgroup analysis that utilizing ITK-SNAP as a segmentation software contributed to a significantly higher pooled sensitivity., Conclusion: This meta-analysis indicates promising diagnostic accuracy of radiomics in predicting Ki-67 in NSCLC., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: In January 2020, WHO declared the 2019 Coronavirus Disease (COVID-19) a pandemic. Though COVID-19 vaccines are recommended, ongoing surveillance is crucial due to potential unforeseen events. Evaluation of long-term effectiveness and safety and addressing emerging variants are vital. This study integrates systematic reviews to assess COVID-19 vaccine efficacy, immunogenicity, and safety comprehensively., Methods: This study was an umbrella review study on the feasibility and effectiveness of vaccines for COVID-19. We conducted a comprehensive search in PubMed, Web of Sciences, and Scopus, using MeSH terms and keywords related to COVID-19 vaccines. Inclusion criteria comprised peer-reviewed systematic reviews and meta-analyses in English, focusing on feasibility and effectiveness. Exclusion criteria targeted non-systematic reviews exclusively on vaccine safety and duplicates. Two independent reviewers screened and resolved discrepancies. Data extraction included key details. Methodological quality was assessed using the ROBIS tool. Data synthesis involves narrative and, if applicable, quantitative synthesis (meta-analysis). Reporting followed PRISMA guidelines., Results: A total of 32 systematic reviews were included in the study, of which 20 also conducted a meta-analysis. The studies investigated in the included reviews ranged from 7 to 74. The included articles were conducted in various countries around the globe. The findings indicated that COVID-19 vaccines are generally safe and effective for individuals with various medical conditions. The overall risk of bias for the included studies was assessed as low risk., Conclusion: The study outcomes indicated that mRNA vaccines exhibit a higher incidence of adverse events but demonstrate greater efficacy. Conversely, inactivated and protein subunit vaccines are safer but exhibit lower efficiency. Moreover, the vaccine is considered safe for individuals with specific conditions such as inflammatory bowel disease, solid organ transplant recipients, children, pregnant individuals, and those with hematologic problems. Ultimately, the acceptance of the COVID-19 vaccine among individuals is influenced by various factors, including geographic, socioeconomic, and pandemic-related considerations., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this manuscript.

This study aimed to evaluate chitosan (CS)-based formulations loaded with 5% sodium fluoride (NaF) and/or 10% nanohydroxyapatite (nHA) to remineralize the demineralized primary tooth enamel surface. Ninety enamel blocks were demineralized and were divided into six groups (n = 15): (1) CS-based hydrogel, (2) CS-based hydrogel loaded with NaF, (3) CS-based hydrogel loaded with nHA, (4) CS-based hydrogel loaded with NaF and nHA, (5) 5% NaF varnish, and (6) negative control with no intervention. After intervention, the specimens were pH cycled by 2 h immersion in demineralizing solution and 22 h immersion in remineralizing solution for 8 days. The remineralization effects were evaluated by Vickers microhardness measurements and field emission scanning electron microscopy coupled with energy-dispersive X-ray spectrometry (FESEM-EDS). The best mean ± SD percentage microhardness recovery in remineralized enamel (%REMH) was found in group 4 (56.90 ± 5.49). The %REMH of groups 2 (30.74 ± 3.51) and 5 (29.23 ± 5.65) were statistically the same (p = 0.943). FESEM images confirmed partial coverage of the porous demineralized enamel with a newly formed mineralized layer. Based on EDS findings, the Ca/P ratio values of the treated enamel surfaces with CS-based hydrogels ranged between 1.71 and 1.87, and the highest F content was noticed in group 2 (1.02 ± 0.03). Although, all tested CS-based hydrogels demonstrated the potential to repair demineralized enamel, nHA- and NaF-containing CS-based hydrogel showed the highest remineralization effect. We infer that this new hybrid hydrogel is a potentially useful dental material for tooth biomineralization., (© 2024. The Author(s).)

The current treatment for oral inflammatory ulcerative diseases has limitations. In situ forming hydrogels have shown great potential to deliver therapeutic substances for drug delivery to the buccal cavity. This study aimed to prepare and characterize lipid- and surfactant-based mixed micelle in situ gel (MIG) and evaluate whether it can offer more favorable properties than the in situ gel for effective treatment of the disease. Dexamethasone was incorporated into the MIGs particles, based on Poloxamer 407 and chitosan. The lower gelation time at 37 ℃ was considered a criterion to select superior formulations among the different lipid- and surfactant-based candidates. Further characterization was performed to evaluate the opted formulations regarding morphology, physical stability, rheology, texture, and release profile. All formulations were thermoresponsive and had a shorter gelation time as the temperature increased. Dexamethasone was released in a highly controlled manner, and morphological evaluation revealed that the mixed micelle in situ gels had spherical nanoparticles. Thixotropic behavior was observed in all MIGs, indicating a prolonged retention time of the formulation after oral administration. This study has shown that among different MIGs, the one with oleic acid is a more promising candidate than the in situ gel and other MIGs for drug delivery to the buccal cavity., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

This cross-sectional study assessed the knowledge, attitude, and practices (KAP) regarding skin cancer among dermatology clinic patients, medical students, and general practitioners (GPs) in Tehran, Iran. The researchers collected data using a validated questionnaire administered online, measuring KAP on scales of 0-31, 0-16, and 0-28, respectively, with scores above 16, 8, and 14 indicating "good" levels. Of 2243 participants (mean age 28 years), 59.4% had good knowledge, 19.8% had good attitudes, 31.8% had good practices, and 29.8% had good overall KAP. Medical students/GPs scored higher on knowledge and attitudes, while patients scored better on practices. Knowledge, attitudes, and practices were positively correlated in professionals but inversely correlated in patients. The findings suggest that while knowledge was moderate, attitudes and behaviors remained poor, particularly among patients. Immediate interventions are needed to improve attitudes and prevention practices, as public health initiatives must focus on positively influencing both to translate knowledge into meaningful action and find the reasons why good knowledge may not always lead to good practice. These findings underline the need for targeted interventions to bridge the gap between knowledge and preventive behaviors, to effectively reduce the burden of skin cancer in the population., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this study., (Copyright © 2024 Moein Baghani et al.)

Background: Pemphigus is a group of autoimmune blistering disorders that have been associated with dementia in previous studies. Mild cognitive impairment (MCI) can be the first stage of progression into dementia. The objective of the present study was to evaluate the frequency of MCI in pemphigus patients compared to a control group., Methods: This case-control study included 80 patients with pemphigus referred to the dermatology clinics of Shohadaye Tajrish and Loghman Hakim hospitals, Tehran, Iran, in 2021. A group of 80 individuals without pemphigus who visited the same clinics for cosmetic consultation or interventions were regarded as controls. Age, sex, marital status, and education were recorded for all participants. Disease duration, medications, and severity were noted for pemphigus patients. The Persian version of the Montreal Cognitive Assessment (MoCA) test was used to assess cognitive function., Results: MCI was significantly more frequent in pemphigus patients than in controls (55% vs. 37.5%, P = 0.026). Furthermore, the total MoCA score was significantly lower in pemphigus patients compared to controls (23.98 ± 3.77 vs. 25.21 ± 3.45, P = 0.032); however, among MoCA's different domains, only the executive functions score was significantly lower in pemphigus patients (P = 0.010). After adjustment, multivariable logistic regression analysis revealed that every 1-year higher education in patients decreased the odds of MCI by 52% (adjusted odds ratio = 0.483, 95% confidence interval 0.326; 0.715, P < 0.001)., Conclusions: The frequency of MCI was found to be significantly higher, and overall scores of the MoCA test, as well as its executive function domain, were significantly lower among pemphigus patients in this study compared to the control group. Additionally, a higher level of education was associated with decreased odds of MCI in pemphigus patients. Identifying pemphigus patients with MCI through the use of the MoCA test can facilitate early intervention, enabling them to seek help and support., (© 2024 the International Society of Dermatology.)

Biomaterials possess distinctive properties, notably their ability to encapsulate active biological products while providing biocompatible support. The immune system plays a vital role in preventing cancer recurrence, and there is considerable demand for an effective strategy to prevent cancer recurrence, necessitating effective strategies to address this concern. This review elucidates crucial cellular signaling pathways in cancer recurrence. Furthermore, it underscores the potential of biomaterial-based tools in averting or inhibiting cancer recurrence by modulating the immune system. Diverse biomaterials, including hydrogels, particles, films, microneedles, etc., exhibit promising capabilities in mitigating cancer recurrence. These materials are compelling candidates for cancer immunotherapy, offering in situ immunostimulatory activity through transdermal, implantable, and injectable devices. They function by reshaping the tumor microenvironment and impeding tumor growth by reducing immunosuppression. Biomaterials facilitate alterations in biodistribution, release kinetics, and colocalization of immunostimulatory agents, enhancing the safety and efficacy of therapy. Additionally, how the method addresses the limitations of other therapeutic approaches is discussed.

Background: Triamcinolone acetate injections are considered the first treatment option for keloids, but quite high proportions of keloids either do not respond to triamcinolone or develop recurrence. Beneficial effects of intralesional bleomycin have been recently shown in the treatment of keloids and hypertrophic scars. However, the efficacy of combination therapy using intralesional triamcinolone and bleomycin remains undetermined., Objective: The purpose of this study was to evaluate the efficacy of using bleomycin and triamcinolone mixture to treat refractory keloids., Materials and Methods: In total, 33 patients with resistant keloids (including 8 men and 25 women) and a mean age of 36.52 years (age range of 18-65 years) were enrolled in this study. A mixture of bleomycin (1 u/cc) with triamcinolone acetonide (13.3 mg/cc) was injected intralesionally into the keloids every 4 to 6 weeks for a maximum of 6 cycles. The clinical improvement was evaluated using the Japan Scar Scale (JSS) and the physician's global assessment of the flattening of the lesions. Side effects were also noted and recorded., Results: In all patients, the total JSS scores decreased significantly after treatment (2.33 ± 1.05), compared with baseline (11.61 ± 2.59), ( p < .001); 26 keloids (78.8%) showed an excellent response (75%-100% flattening), 7 keloids (21.2%) showed a fair response (25%-75% flattening), and 0 keloids (0%) showed a poor response (<25% flattening). Observed side effects were ulceration (33.3%), hyperpigmentation (33.3%), hypopigmentation (15.15%), secondary infection (33.3%), and telangiectasis (15.15%)., Conclusion: The combined use of bleomycin and triamcinolone offers a promising treatment option for individuals who have not responded well to traditional therapies., (Copyright © 2023 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

The development of remineralizing smart biomaterials is a contemporary approach to caries prevention. The present study aimed at formulation preparation and characterization of a thermoresponsive oral gel based on poloxamer and chitosan loaded with sodium fluoride (NaF) and nanohydroxyapatite (nHA) to treat demineralization. The chemical structure and morphology of the formulation were characterized using FTIR and FESEM-EDS tests. Hydrogel texture, rheology, and stability were also examined. The hydrogel was in a sol state at room temperature and became gel after being placed at 37 °C with no significance different in gelation time with the formulation without nHA and NaF as observed by t -test. The FTIR spectrum of nHA/NaF/chitosan-based hydrogel indicated the formation of physical crosslinking without any chemical interactions between the hydrogel components. The FESEM-EDS results demonstrated the uniform distribution of each element within the hydrogel matrix, confirming the successful incorporation of nHA and NaF in the prepared gel. The hardness, hydrogel's adhesiveness, and cohesiveness were 0.9 mJ, 1.7 mJ, and 0.37, respectively, indicating gel stability and the acceptable retention time of hydrogels. The formulation exhibited a non-Newtonian shear-thinning pseudoplastic and thixotropic behavior with absolute physical stability. Within the limitation of in vitro studies, nHA/NaF/chitosan-based in situ forming gel demonstrated favorable properties, which could be trasnsorm into a gel state in oral cavity due to poloxamer and chitosan and can prevent dental caries due to nHA and NaF. We propose this formulation as a promising dental material in tooth surface remineralization., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: We aimed to investigate the effects of nerve repair by setting a side-to-side (H-shaped) nerve graft on the most distal part of the damaged nerve to the adjacent intact nerve to accelerate its regeneration in the end organ., Methods: This pure experimental study was done on the lower extremities of two groups of rabbits in Animal Laboratory Department, 15 Khordad Hospital Tehran, Iran. In both groups, the sciatic nerve at the proximal part of the extremity below the superficial femoral branch was first cut and then repaired. In the investigation group, side-to-side H-shaped nerve grafts were applied between the sciatic and superficial femoral nerves (i.e., two branches) at the most distal to the cut site of the sciatic nerve below the superficial femoral branch at the lower extremity. The sciatic nerve was conventionally repaired in the control group., Results: None of the rabbits' feet in the control group respond to pain stimulation (were without senses) and had ulcers. They had numb legs and went lame. All had muscular atrophy and lacked nerve growth (regeneration) according to pathology. In the investigation group, 86.7% of the rabbits responded to pain stimulation and only 13.3% of them had ulcers. In addition, in pathology report, 13.3% had suffered muscular atrophy and lacked nerve regeneration. Therefore, nerve regeneration was successful in 86.7% of rabbits who underwent H-shaped nerve grafts., Conclusion: Side-to-side H-shaped nerve graft at the most distal part of an injured nerve may cause successful recovery of high (proximal) nerve injury., Competing Interests: The authors attest that they have no conflict of interest to disclose.

Congenital cleft lip and palate represent the prevailing craniofacial birth anomalies on a global scale. Notably, a substantial proportion of patients within remote regions of Iran defer corrective surgery until later stages of life, often in childhood or adulthood, primarily due to intricate financial and cultural constraints. In response to this pressing healthcare challenge, a dedicated collective of volunteer plastic surgeons was established in 2009 with the explicit aim of providing medical care to these underserved patients. Over the subsequent years, this compassionate team embarked on 31 meticulously planned missions to underprivileged areas scattered across the country. Through these organized endeavors, a remarkable total of 20,579 medical visits were conducted, coupled with the performance of 2,303 essential surgeries, thus offering a lifeline of healthcare to these disadvantaged individuals., Competing Interests: None declared.

Friedreich's ataxia (FRDA) is caused by expansions of GAA•TTC repeats in the first intron of the human FXN gene that occur during both intergenerational transmissions and in somatic cells. Here we describe an experimental system to analyze large-scale repeat expansions in cultured human cells. It employs a shuttle plasmid that can replicate from the SV40 origin in human cells or be stably maintained in S. cerevisiae utilizing ARS4-CEN6. It also contains a selectable cassette allowing us to detect repeat expansions that accumulated in human cells upon plasmid transformation into yeast. We indeed observed massive expansions of GAA•TTC repeats, making it the first genetically tractable experimental system to study large-scale repeat expansions in human cells. Further, GAA•TTC repeats stall replication fork progression, while the frequency of repeat expansions appears to depend on proteins implicated in replication fork stalling, reversal, and restart. Locked nucleic acid (LNA)-DNA mixmer oligonucleotides and peptide nucleic acid (PNA) oligomers, which interfere with triplex formation at GAA•TTC repeats in vitro, prevented the expansion of these repeats in human cells. We hypothesize, therefore, that triplex formation by GAA•TTC repeats stall replication fork progression, ultimately leading to repeat expansions during replication fork restart., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Cell-based drug delivery systems are new strategies in targeted delivery in which cells or cell-membrane-derived systems are used as carriers and release their cargo in a controlled manner. Recently, great attention has been directed to cells as carrier systems for treating several diseases. There are various challenges in the development of cell-based drug delivery systems. The prediction of the properties of these platforms is a prerequisite step in their development to reduce undesirable effects. Integrating nanotechnology and artificial intelligence leads to more innovative technologies. Artificial intelligence quickly mines data and makes decisions more quickly and accurately. Machine learning as a subset of the broader artificial intelligence has been used in nanomedicine to design safer nanomaterials. Here, how challenges of developing cell-based drug delivery systems can be solved with potential predictive models of artificial intelligence and machine learning is portrayed. The most famous cell-based drug delivery systems and their challenges are described. Last but not least, artificial intelligence and most of its types used in nanomedicine are highlighted. The present Review has shown the challenges of developing cells or their derivatives as carriers and how they can be used with potential predictive models of artificial intelligence and machine learning.

One of the practical ways to manage the disease flares of arthritis is using an intra-articular depot formulation of glucocorticoids. Hydrogels, as controllable drug delivery systems, are hydrophilic polymers with distinctive properties, such as remarkable water capacity and biocompatibility. This study aimed to design an injectable thermo-ultrasound-triggered drug carrier based on Pluronic® F-127, hyaluronic acid, and gelatin. The in situ hydrogel loaded by hydrocortison was developed and D-optimal design was used to formulate the process. The optimized hydrogel was combined with four different surfactants to better regulate the release rate. In situ gels composed of the hydrocortisone-loaded hydrogel and hydrocortisone-loaded mixed-micelle hydrogel were characterized. The hydrocortisone-loaded hydrogel and selected hydrocortisone-loaded mixed-micelle hydrogel showed a spherical shape and were nano-sized with a unique thermo-responsive nature able to prolong drug release. The ultrasound-triggered release study showed that drug release was time-dependent. By inducing osteoarthritis in a rat model, behavioral tests and histopathological analyses were carried out on the hydrocortisone-loaded hydrogel and a particular hydrocortisone-loaded mixed-micelle hydrogel. In vivo results showed that the selected hydrocortisone-loaded mixed-micelle hydrogel improved the status of the disease. Results highlighted the potential of ultrasound-responsive in situ-forming hydrogels as hopeful formulas for efficient treatment of arthritis., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Glioma is an intra-cranial malignancy with the origin of neural stem cells or precursor cells, the most prevalent brain tumor worldwide. Glioblastoma, the fourth-grade glioma, is a common brain tumor whose incidence rate is 5-7 people per 100,000 populations annually. Despite their high mortality rate, all efforts for treatment have yet to achieve any desirable clinical outcome. The Wnt signaling pathway is a conserved pathway among species that seems to be a candidate for cancer therapy by its inhibition. Metformin is a known inhibitor of the Wnt signaling pathway. Its effects on glioma treatment have been observed in cellular, animal, and clinical experiments. Nanoerythrosomes are drug carriers obtained from the cellular membrane of red blood cells in nano size which can offer several characteristics to deliver metformin to brain tumors. They are good at loading and carrying hydrophilic drugs, they can protect metformin from its metabolizing enzymes, which are present in the blood-brain barrier, and they can extend the period of metformin presence in circulation. In this study, nanoerythrosomes were prepared by using the hypotonic buffer. They had particle sizes in the range of 97.1 ± 34.2 nm, and their loading efficiency and loading capacity were 72.6% and 1.66%, respectively. Nanoerythrosomes could reserve metformin in their structure for a long time, and only 50% of metformin was released after 30 h. Moreover, they released metformin at a low and approximately constant rate. Besides, nanoerythrosomes could tolerate various kinds of stress and maintain most of the drug in their structure. Altogether, nanoerythrosome can be a suitable drug delivery system to deliver therapeutic amounts of metformin to various tissues., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Huntington's disease is a neurodegenerative, trinucleotide repeat (TNR) disorder affecting both males and females. It is caused by an abnormal increase in the length of CAG•CTG TNR in exon 1 of the Huntingtin gene ( HTT ). The resultant, mutant HTT mRNA and protein cause neuronal toxicity, suggesting that reduction of their levels would constitute a promising therapeutic approach. We previously reported a novel strategy in which chemically modified oligonucleotides (ONs) directly target chromosomal DNA. These anti-gene ONs were able to downregulate both HTT mRNA and protein. In this study, various locked nucleic acid (LNA)/DNA mixmer anti-gene ONs were tested to investigate the effects of varying ON length, LNA content, and fatty acid modification on HTT expression. Altering the length did not significantly influence the ON potency, while LNA content was critical for activity. Utilization of palmitoyl-modified LNA monomers enhanced the ON activity relatively to the corresponding nonmodified LNA under serum starvation conditions. Furthermore, the number of palmitoylated LNA monomers and their positioning greatly affected ON potency. In addition, we performed RNA sequencing analysis, which showed that the anti-gene ONs affect the "immune system process, mRNA processing, and neurogenesis." Furthermore, we observed that for repeat containing genes, there is a higher tendency for antisense off-targeting. Taken together, our findings provide an optimized design of anti-gene ONs that could potentially be developed as DNA-targeting therapeutics for this class of TNR-related diseases.