OBJECTIVE: To entrap carvacrol (CAR) in bovine serum albumin nanoparticles (BSANPs) to form CAR-loaded BSANPs (CAR@BSANPs) and to explore the anti-cancer effects in breast adenocarcinoma cells (MCF-7 cells) treated with CAR and CAR@BSANPs. METHODS: A desolvation method was used to synthesize BSANPs and CAR@BSANPs. The BSANPs and CAR@BSANPs were characterized by several physicochemical methods, including visual observation, high-resolution field emission scanning electron microscopy, Fourier transform infrared spectroscopy, and high-performance liquid chromatography. MCF-7 cells were used and analyzed after 24 h of exposure to CAR and CAR@BSANPs at half-maximal inhibitory concentration. The anti-proliferative, apoptotic, reactive oxygen species (ROS), and nitric oxide (NO) scavenging activity as well as gene expression analysis were investigated by the cell viability assay, phase-contrast microscopy, 2',7'-dichlorofluorescein-diacetate assay, Griess-Illosvoy colorimetric assay, and quantitative real-time polymerase chain reaction, respectively. RESULTS: CAR and CAR@BSANPs showed anti-proliferative, apoptotic, ROS generation, and NO scavenging effects on MCF-7 cells. Expression profile of B-cell lymphoma 2-like 11 (BCL2L11), vascular endothelial growth factor A (VEGFA), hypoxia inducible factor factor-1α (HIF1A), BCL2L11/apoptosis regulator (BAX), and BCL2L11/Bcl2 homologous antagonist/killer 1 (BAK1) ratios revealed downregulated genes; and BAX, BAK1, and CASP8 were upregulated by CAR and CAR@BSANPs treatment. In vitro anticancer assays of the CAR and CAR@BSANPs showed that CAR@BSANPs demonstrated higher therapeutic efficacy in the MCF-7 cells than CAR. CONCLUSIONS CAR and CAR@BSANPs affect gene expression and may subsequently reduce the growth and proliferation of the MCF-7 cells. Molecular targeting of regulatory genes of the MCF-7 cells with CAR and CAR@BSANPs may be an effective therapeutic strategy against breast cancer.
Humans ; Cymenes ; Nanoparticles/ultrastructure* ; MCF-7 Cells ; Breast Neoplasms/genetics* ; Apoptosis/drug effects* ; Serum Albumin, Bovine/chemistry* ; Monoterpenes/therapeutic use* ; Adenocarcinoma/genetics* ; Cell Proliferation/drug effects* ; Reactive Oxygen Species/metabolism* ; Female ; Cell Survival/drug effects* ; Animals ; Gene Expression Regulation, Neoplastic/drug effects* ; Nitric Oxide/metabolism* ; Cattle

Purpose: This study aimed to investigate the efficacy of hydrocortisone enema in preventing radiation proctitis in patients with rectal cancer undergoing short-course radiotherapy (SCRT). Methods: This phase II randomized controlled trial enrolled patients with newly diagnosed locally advanced rectal cancer (clinically staged T3–4 and/or N1–2M0). Participants received a median of 4 cycles of neoadjuvant chemotherapy (capecitabine plus oxaliplatin) followed by 3-dimensional conformal SCRT (25 Gy in 5 fractions). Patients were randomly assigned to receive either a hydrocortisone enema (n=50) or a placebo (n=51) once daily for 5 consecutive days during SCRT. The primary endpoint was the incidence and severity of acute proctitis. Results: Of the 111 eligible patients, 101 were included in the study. Baseline characteristics, including sex, age, performance status, and tumor location, were comparable across the treatment arms. None of the patients experienced grade 4 acute gastrointestinal toxicity or had to discontinue treatment due to treatment-related adverse effects. Patients in the hydrocortisone arm experienced significantly less severe proctitis (P<0.001), diarrhea (P=0.023), and rectal pain (P<0.001) than those in the placebo arm. Additionally, the duration of acute gastrointestinal toxicity following SCRT was significantly shorter in patients receiving hydrocortisone (P<0.001). Conclusion Hydrocortisone enema was associated with a significant reduction in the severity of proctitis, diarrhea, and rectal pain compared to placebo. Additionally, patients treated with hydrocortisone experienced shorter durations of gastrointestinal toxicity following SCRT. This study highlights the potential benefits of hydrocortisone enema in managing radiation-induced toxicity in rectal cancer patients undergoing radiotherapy.

Introduction: The HBC-HBP Scale is the most common scale for measuring adherence to medication in the elderly with hypertension, its Persian version has never been tested in Iran. Methods: 281 older adults with hypertension were randomly selected from health care centers in Iran during the second half-year of 2019. The demographic questionnaire and Persian, Turkmen, and Kazak versions of HBC-HBP were completed by participants. The scale structure was evaluated using goodness of fit by Exploratory and Confirmatory Factor Analysis using IBM-SPSS v.26 and AMOS v.24. Results: The mean of CVI was 0.94, indicating good content validity for HBC-HBP. Exploratory Factor Analysis revealed two subscales for HBC-HBP, collectively explaining 70% of the adherence medication variance in three versions. All item loadings were “moderate” to “excellent”, ranging from 0.38 (Moderate) to 0.95(excellent). Confirmatory Factor Analysis indicated the goodness of fit for the HBC-HBP based on the trilingual version. A high goodness of fit was sown for Turkmen, Persian, and Kazak versions of HBC-HBP. (Chi-Square=8.213, 8.354, 8.210, RMSEA=0.016, 0.013, 0.010, GFI=0.90, 0.90, 0.91, CFI=0.91, 0.90, 0.91, and AGFI=0.90, 0.91, 0.90). Cronbach’s alpha was 0.90 for the whole scale (p<0.001). The optimal cut-off point that best distinguished between adherent and non-adherent patients was 26.5. Conclusion: Results showed the validity and reliability of the trilingual versions of the HBMA for measuring adherence medication in the elderly with hypertension.

Purpose: This study was performed to investigate the efficacy and safety of short-course radiation therapy (SCRT) and sequential chemotherapy followed by delayed surgery in locally advancer rectal cancer with subgroup analysis between the older and young patients. Materials and Methods: In this single-arm phase II clinical trial, eligible patients with locally advanced rectal cancer (T3–4 and/or N1–2) were enrolled. All the patients received a median three sequential cycles of neoadjuvant CAPEOX (capecitabine + oxaliplatin) chemotherapy. A total dose of 25 Gy in five fractions during 1 week was prescribed to the gross tumor and regional lymph nodes. Surgery was performed about 8 weeks following radiotherapy. Pathologic complete response rate (pCR) and grade 3–4 toxicity were compared between older patients (≥65 years) and younger patients (<65 years). Results: Ninety-six patients with locally advanced rectal cancer were enrolled. There were 32 older patients and 64 younger patients. Overall pCR was 20.8% for all the patients. Older patients achieved similar pCR rate (18.7% vs. 21.8; p = 0.795) compared to younger patients. There was no statistically significance in terms of the tumor and the node downstaging or treatment-related toxicity between older patients and younger ones; however, the rate of sphincter-saving surgery was significantly more frequent in younger patients (73% vs. 53%; p=0.047) compared to older ones. All treatment-related toxicities were manageable and tolerable among older patients. Conclusion Neoadjuvant SCRT and sequential chemotherapy followed by delayed surgery was safe and effective in older patients compared to young patients with locally advanced rectal cancer.

PURPOSE: Currently, neoadjuvant chemoradiation (CRT) followed by total mesorectal resection is considered the standard of care for treating locally advanced rectal cancer. This study aimed to investigate the efficacy and feasibility of adding induction chemotherapy to neoadjuvant CRT in locally advanced rectal cancer. METHODS: This phase-II clinical trial included 54 patients with newly diagnosed, locally advanced (clinical T3–4 and/or N1–2, M0) rectal cancer. All patients were treated with 3 cycles of preoperative chemotherapy using the XELOX (capecitabine + oxaliplatin) regimen before and after a concurrent standard long course of CRT (45–50.4 Gy) followed by standard radical surgery. Pathologic complete response (PCR) rate and toxicity were the primary and secondary end-points, respectively. RESULTS: The study participants included 37 males and 17 females, with a median age of 59 years (range, 20–80 years). Twenty-nine patients (54%) had clinical stage-II disease, and 25 patients (46%) had clinical stage-III disease. Larger tumor size (P = 0.006) and distal rectal location (P = 0.009) showed lower PCR compared to smaller tumor size and upper rectal location. Pathologic examinations showed significant tumor regression (6.1 ± 2.7 cm vs. 1.9 ± 1.8 cm, P < 0.001) with 10 PCRs (18.5%) compared to before the intervention. The surgical margin was free of cancer in 52 patients (96.3%). Treatment-related toxicities were easily tolerated, and all patients completed their planned treatment without interruption. Grade III and IV toxicities were infrequent. CONCLUSION: The addition of induction chemotherapy to neoadjuvant CRT is an effective and well-tolerated treatment approach in patients with rectal cancer.
Drug Therapy ; Female ; Humans ; Induction Chemotherapy ; Male ; Neoadjuvant Therapy ; Polymerase Chain Reaction ; Rectal Neoplasms ; Standard of Care

Objective: To appraise the activity of voriconazole against Leishmania major (L. major) in vitro and its effectiveness on wound regeneration in cutaneous leishmaniasis in BALB/c mice. Methods: The IC

BACKGROUND: Additional cytogenetic aberrations are associated with disease progression in chronic myeloid leukemia (CML). This study was conducted to determine the type and frequency of these aberrations and their relationship with hematologic and molecular findings in the Middle East. METHODS: In this retrospective study, 134 well-established cases of CML were selected from 2010 to 2016. Their hematologic phase and type of fusion gene were determined. Finally, their karyotypes were analyzed and reported according to ISCN 2013. RESULTS: Patients had a mean age of 44 years. Twenty-two patients (16.4%) showed additional cytogenetic aberrations. Nine patients (6.7%) harbored a variant Philadelphia chromosome, and most were in the chronic phase. Seventeen patients (12.7%) had major and minor route abnormalities. There was a significant relationship between additional cytogenetic aberrations and major molecular response (P=0.032). Patient survival in the group with additional cytogenetic aberrations was significantly lower (49.7±11.1 mo) than that in the group without additional cytogenetic aberrations (77.3±3.1 mo) (P=0.031). CONCLUSION: This study revealed the same frequency of additional cytogenetic aberrations in CML as found in previous studies. Additional chromosomal aberrations led to shorter survival and lower rates of achievement of a major molecular response.
Chromosome Aberrations* ; Cytogenetics* ; Disease Progression ; Humans ; Karyotype ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Middle East* ; Philadelphia Chromosome ; Retrospective Studies

BACKGROUND: Production of immunosuppressive enzymes such as indoleamine 2,3-dioxygenase (IDO) is one of the strategies employed by hematologic malignancies, including acute myeloid leukemia (AML), to circumvent immune surveillance. Moreover, IDO has the ability to convert CD4+CD25− conventional T cells into regulatory T cells (Tregs). In this study, we evaluated the expression of IDO in cytogenetically normal acute myeloid leukemia (CN-AML) patients and its correlation with the Treg marker, FOXP3, as well as clinical and laboratory parameters. METHODS: Thirty-seven newly diagnosed CN-AML patients were enrolled in our study along with 22 healthy individuals. The expression of the IDO and FOXP3 genes was analyzed by SYBR Green real-time PCR. RESULTS: Both IDO and FOXP3 were highly upregulated in CN-AML patients compared to control groups (P=0.004 and P=0.031, respectively). A positive correlation was observed between IDO and FOXP3 expression among AML patients (r=0.512, P=0.001). Expression of IDO and FOXP3 showed no significant correlation with laboratory parameters such as white blood cell and platelet counts, hemoglobin levels, bone marrow blast percentage, gender, and FLT3 mutation status (P>0.05). CONCLUSION: Higher IDO expression in CN-AML patients may be associated with an increased Treg phenotype which may promote disease progression and lead to poor prognosis of CN-AML patients.
Bone Marrow ; Disease Progression ; Hematologic Neoplasms ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase* ; Karyotype* ; Leukemia, Myeloid, Acute* ; Leukocytes ; Phenotype* ; Platelet Count ; Prognosis ; Real-Time Polymerase Chain Reaction ; T-Lymphocytes ; T-Lymphocytes, Regulatory

PURPOSETraffic injuries are among the leading causes of mortality and morbidity worldwide. Pedestrians have been considered as a high-risk group among road users, especially in middle- or low-income communities. This study attempted to determine the burden of pedestrians' fatalities in Fars, the southern province of Iran using years of life lost (YLL) approach.

METHODSThe data used in this study were retrieved from Fars Forensic Medicine Organization database on pedestrian traffic accidents. The YLL from 2009 to 2013 was estimated using the method presented by World Health organization. Some epidemiological characteristics of pedestrians' fatalities were analyzed by SPSS.

RESULTSAlthough YLL among 1000 male pedestrians decreased from 2.5 in 2009 to 1.5 in 2013, it increased from 0.9 to 2.1 among 1000 females during the same period. Higher proportion of death was found in female, illiterate, and married pedestrians (p < 0.001). In addition, mortality was higher in pedestrians living the cities, during daytime, at home, and in hospitals (p < 0.001).

CONCLUSIONConsistent with the global trends, burden of pedestrian accidents in Fars was also exceptionally high. Considering the national and cultural aspects of different countries, improving the safety of pedestrians demands a multi-dimensional approach with interventional factors concerning policies, rules, pedestrians, motor vehicles and environmental conditions taken into consideration.

PURPOSEUnsafe behaviors are an important cause of accidents in adolescent age groups. This study was designed to examine the behaviors of adolescent pedestrians in southern Iran.

METHODSThis is a descriptive analytical cross-sectional study. The study population consisted of high school students in Shiraz, capital city of Fars Province, Iran. Five hundred and sixteen students were selected by multi-stage sampling. Data were collected by the use of three questionnaires, which included Persian copies of adolescent road user behavior questionnaire (ARBQ), Duke University Religious Index (DUREL), as well as the context and independent variables questionnaire.

RESULTSThe results showed that a decrease in dangerous behaviors on the road resulted in an increase in respondents' intrinsic religiosity. Also, engagement in unsafe crossing behavior in the road decreased with increasing respondents' intrinsic religiosity. Another finding showed that female students were less involved in dangerous play and planned protective behaviors on the road.

CONCLUSIONFindings clearly indicate that intrinsic religiosity has a significant role in reducing the risky road behaviors of students. Hence, religion may improve road safety in school students' road behavior in Iran.