Quantitative analysis of biochemical characteristics and anti-cancer properties in MCF-7 breast cancer cell line: a comparative study between Ziziphus jujube honey and commercial honey.

BACKGROUND: There is increasing evidence that honey has anti-inflammatory, antioxidant, and anti-cancer effects. This study aims to assess and contrast the cytotoxic, anti-metastatic, and apoptotic effects of Ziziphus jujube honey and commercial honey on MCF7 cells. METHODS AND RESULTS: Two honey samples, Ziziphus jujube (JH) and commercial honey (CH), were categorized into high and low groups based on their phenolic content, antioxidant capacity, and diastase activity (PAD score). The viability and migration ability of MCF-7 cells treated with JH and CH were evaluated. Also, quantitative polymerase chain reaction (Q-PCR) was performed to assess the effect of the two honey samples on the expression of Bax, p53, p21 and Bcl-2 genes. JH had a total phenolic content of 606.4 ± 0.1 µg gallic acid equivalent/mg, while CH had a value of 112.1 ± 0.09 µg gallic acid equivalent/mg. The total antioxidant capacity of the two samples was compared. It was 203.5 ± 10.5µM/l in JH and 4.6 ± 10.5 µM/l in CH. In addition, JH had a diastatic activity of 524.1 ± 0.25 U/l, while CH had a value of 209.7 ± 0.56 U/l. According to the results, JH had a high PAD value, while CH had a low PAD value. Cell viability was measured using the results of the MTT assay. The results showed that JH inhibited the growth of MCF-7 cells more strongly (IC50 of 170 ± 4.2 µg/ml) than CH (IC50 of 385.3 ± 4.5 µg/l). The scratch assay showed that treatment with JH decreased the migration rate of MCF-7 cells in a dose-dependent manner compared to the CH and control groups. In addition, the results of q-PCR analysis showed significant upregulation of Bax, p53 and p21 genes and downregulation of Bcl-2 gene in the JH-treated group compared to the CH and control groups. CONCLUSION: These results showed that honey with an increased content of phenolic compounds, antioxidant capacity, and diastatic activity has anticancer properties by effectively suppressing tumor development. This suppression occurs via several mechanisms, including suppression of proliferation and metastasis, and promotion of apoptosis.

Effect of Elaeagnus Angustifolia extract on in vitro wound healing of human dermal fibroblast cells.

AIM: The purpose of this study was to determine the impact of Elaeagnus Angustifolia extract (EA) on human dermal fibroblast (HDF) survival, migration, and wound healing-related genes. METHODS: After preparing the hydroalcoholic extract of EA, MTT and scratch tests were used to determine the effect of EA on the viability and migration of HDFs. In addition, the quantitative polymerase chain reaction (q-PCR) was conducted to evaluate the impact of EA on the expression of wound healing-related genes in HDFs. RESULT: According to the MTT test, a nontoxic concentration of EA (100 µg/ml) was obtained for further investigations. The scratch test results demonstrated that EA improved HDFs' capacity to migrate when compared to the control group. Additionally, q-PCR results revealed that EA could significantly increase wound healing-related genes (VEGF-A, HLA-G5, and IL-6) in comparison with the control group. CONCLUSIONS: The EA could have a significant impact on the viability and migration of HDFs. Also, EA increased the expression of wound healing-related genes.

Green synthesis of nanohydroxyapatite trough Elaeagnus angustifolia L. extract and evaluating its anti-tumor properties in MCF7 breast cancer cell line.

BACKGROUND: One of the most common types of cancer in women is breast cancer. There are numerous natural plant-based products, which exert anti-tumoral effects including Elaeagnus Angustifolia (EA). It modulates cell-cycle process, heat-shock proteins expression, anti-proliferative properties, apoptosis induction, blocking of angiogenesis, and cell invasion inhibition. The current study aimed to synthesize and evaluate the anticancer effects of hydroalcoholic EA extract (HEAE), Nanohydroxyapatite (nHAp) and nHAp synthesized trough EA (nHA-EA) in MCF-7 breast cancer cell line. METHODS: In the present study, HEAE preparation and green synthesis of nHA-EA was done and phase composition, functional groups, and crystallin phase of nHA-EA and nHAp were determined using Fourier-transform infrared (FTIR) and X-ray diffraction (XRD). The characteristics of synthesized nanoparticles including structural and morphological parameters were investigated using scanning electron microscopy (SEM) and Transmission electron microscopy (TEM) techniques. Then, by using MTT-assay (Dimethylthiazoldiphenyltetrazolium), the in vitro cytotoxic and half maximal inhibitory concentration (IC50) of EA extract, nHAp, and nHA-EA in the MCF-7 breast cancer cell line was evaluated. Next, we assessed the expression of apoptosis-related genes Bax, Bcl2 and p53 using quantitative reverse-transcriptase polymerase-chain-reaction (qRT-PCR) and migration of MCF-7 cells by scratch assay. RESULTS: The FTIR results demonstrated formation of nHAp and its interaction with HEAE during synthesis process. The XRD results of the synthesized nanoparticles showed similar XRD pattern of nHA-EA and nHAp and purity of synthesized nanomaterials. The average IC50 of HEAE, nHAp, and nHA-EA extract after treatment of cancer cells for 24 h was 400 µg/mL, 200 µg/mL, and 100 µg/mL, respectively. Our results revealed that nHA-EA significantly reduced the migration and invasion of the MCF-7 cells, in comparison to the nHAp and EA extract. Moreover, level of Bax/Bcl2 and p53 was significantly higher in the nHA-EA extract group in comparison to the EA extract and nHAp group. CONCLUSION: Taken together, our results demonstrated that bioactive constituents of EA medicinal plant in form of nHA-EA particles, can effectively exerts potential anticancer and chemo preventive effect against breast cancer growth and can be proposed as a promising beneficial candidate for BC therapy. However, further investigations are required to discover what bioactive compounds are responsible for the chemo preventive effect of this extract.

Effect of HM-Exos on the migration and inflammatory response of LPS-exposed dental pulp stem cells.

AIM: The purpose of this study was to investigate the effects of human milk exosomes (HM-Exos) on the viability, migration, and inflammatory responses of lipopolysaccharide (LPS)-exposed human dental pulp stem cells (HDPSCs) in vitro. METHODS: HM-Exos were isolated, and dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were used to analyze their physical properties (size and shape). To construct an in vitro inflammation model, HDPSCs were exposed to LPS. The MTT test and migration assay were used to investigate the effect of HM-Exos on cell proliferation and migration, and the quantitative polymerase chain reaction (qPCR) was used to assess the expression of inflammatory genes in HDPSCs. Data were analyzed using a one-way analysis of variance (ANOVA) with Tukey's post-test. RESULTS: DLS measurement revealed that HM-Exos were 116.8 ± 3.6 nm in diameter. The SEM and TEM images revealed spherical shapes with diameters of 97.2 ± 34.6 nm. According to the results of the cell viability assay, the nontoxic concentration of HM-Exos (200 µg/ml) was chosen for the subsequent investigations. The migration assay results showed that HM-Exos improved the potential of LPS-exposed HDPSCs to migrate. The qPCR results indicated that HM-Exos significantly reduced the expression of inflammatory cytokines such as TNF-α, IL-1ß, and IL-6 in HDPSCs after LPS stimulation. CONCLUSIONS: HM-Exos increased LPS-exposed HDPSCs migration and proliferation and reduced gene expression of inflammatory cytokines. They may be a viable candidate for pulpitis therapy.

Dentin regeneration based on tooth tissue engineering: A review.

Missing or damaged teeth due to caries, genetic disorders, oral cancer, or infection may contribute to physical and mental impairment that reduces the quality of life. Despite major progress in dental tissue repair and those replacing missing teeth with prostheses, clinical treatments are not yet entirely satisfactory, as they do not regenerate tissues with natural teeth features. Therefore, much of the focus has centered on tissue engineering (TE) based on dental stem/progenitor cells to create bioengineered dental tissues. Many in vitro and in vivo studies have shown the use of cells in regenerating sections of a tooth or a whole tooth. Tooth tissue engineering (TTE), as a promising method for dental tissue regeneration, can form durable biological substitutes for soft and mineralized dental tissues. The cell-based TE approach, which directly seeds cells and bioactive components onto the biodegradable scaffolds, is currently the most potential method. Three essential components of this strategy are cells, scaffolds, and growth factors (GFs). This study investigates dentin regeneration after an injury such as caries using TE and stem/progenitor cell-based strategies. We begin by discussing about the biological structure of a dentin and dentinogenesis. The engineering of teeth requires knowledge of the processes that underlie the growth of an organ or tissue. Then, the three fundamental requirements for dentin regeneration, namely cell sources, GFs, and scaffolds are covered in the current study, which may ultimately lead to new insights in this field.

Effects of hydroxyapatite nanorods prepared through Elaeagnus Angustifolia extract on modulating immunomodulatory/dentin-pulp regeneration genes in DPSCs.

Dental pulp stem cells (DPSCs) are a new type of mesenchymal stem cells (MSCs) found in the oral cavity with immunomodulation and tissue regeneration capacities. This study determined the impacts of nano-hydroxyapatite (nHA) prepared through Elaeagnus Angustifolia extract (EAE) to enhance the relative expression of immunomodulatory/dentin-pulp regeneration genes in DPSCs. To produce nHA and modified nHA via EAE (nHAEA), the sol-gel technique was used. The functional groups of nanoparticles (NPs), morphological, and optical features were determined using Fourier transform infrared (FTIR), X-ray diffraction (XRD), Scanning electron microscopy (SEM) together with energy-dispersive X-ray analysis (EDAX), and Transmission electron microscopy (TEM). The cell viability was then determined using the MTT method in the presence of various EAE, nHA, and nHAEA concentrations. Target gene expression was quantified using a real-time PCR procedure after treating DPSCs with an optimally non-toxic dose of EAE and NPs. The presence of the HA phase was reported with the XRD and FTIR results. According to the results of SEM and TEM, the rod-like NPs could be fabricated. nHAEAs were found to be characterized with low crystallite size, reduced diameter, lengthier, needle-like, and less agglomerated particles compared with nHA. The real-time PCR results demonstrated that nHAEA remarkably increased the expression of human leukocyte antigen-G5 (HLA-G5), vascular endothelial growth factor (VEGF), dentin sialophosphoprotein (DSPP), and interleukin6 (IL6) genes compared to the nHA group. These findings suggest that nHAEAs might have the potential application in the stemness capability of DPSCs for the treatment of inflamed/damaged pulp.

Effect of PCL/nHAEA nanocomposite to osteo/odontogenic differentiation of dental pulp stem cells.

PURPOSE: The green synthesis of nanoparticles has recently opened up a new route in material production. The aim of this study was to evaluate the effect of nanohydroxyapatite (nHA) synthesized from Elaeagnus angustifolia (EA) extract in polycaprolactone (PCL) nanofibers (PCL/nHAEA) to odontogenic differentiation of dental pulp stem cells (DPSCs) and their potential applications for dentin tissue engineering. METHODS: Green synthesis of nHA via EA extract (nHAEA) was done by the sol-gel technique. Then electrospun nanocomposites containing of PCL blended with nHA (P/nHA) and nHAEA (P/nHAEA) were fabricated, and the characterization was evaluated via X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and the contact angle. The morphology of nanofibers and the cell adhesion capacity of DPSCs on nanofibers were evaluated using SEM. Cytocompatibility was assessed by MTT. Osteo/odontogenic differentiation ability of the nanocomposites were assessed using alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and quantitative real-time polymerase chain reaction (qPCR) technique. RESULTS: Viability and adhesion capacity of DPSCs were higher on P/nHAEA nanofibers than PCL and P/nHA nanofibers. ARS assay, ALP activity, and qPCR analysis findings confirmed that the nHAEA blended nanofibrous scaffolds substantially increased osteo/odontogenic differentiation of DPSCs. CONCLUSION: PCL/nHAEA nanocomposites had a noticeable effect on the odontogenic differentiation of DPSCs and may help to improve cell-based dentin regeneration therapies in the future.

Association between adherence to the dietary approaches to stop hypertension (DASH) diet and maternal and infant sleep disorders.

BACKGROUND: Maternal diet is known to be important to both mother and infant health. The purpose of this study was to evaluate the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) dietary pattern (DP) and sleep problems in mothers and their infants. METHODS: The study included 350 breastfeeding mothers with an average age of 29.5 ± 5.9 years. Psychological functions were performed using standard questionnaires, including a Quality-of-Life Questionnaire (QLQ), Edinburgh Postnatal Depression Scale (EPDS), Spielberger Anxiety Questionnaire (SAQ), Pittsburg Sleep Quality Index (PSQI), and Infant Sleep Questionnaire (ISQ). Also, a standardized food frequency questionnaire (FFQ) was used to identify adherence to the DASH DP. RESULTS: Subjects in the highest tertile of DASH DP had significantly lower scores of mother's sleep latency (0.70 ± 1.18 vs. 1.24 ± 1.3; P value = 0.031), sleep disorders (4.3 ± 1.6 vs. 5.3 ± 2.4; P value= 0.032) and higher mother sleep efficiency compared to those in the lowest tertile (97.5 ± 89 vs. 54.8 ± 90; P value= 0.011). Also, infants of mothers with higher adherence to a DASH DP had lower sleep disorders compared with subjects with low adherence (4.9 ± 3.8 vs. 5.7 ± 3.2; P value= 0.017). After controlling for the mother's education, economic status, age, body mass index (BMI), and energy intake, adherence to the DASH pattern was associated with shorter sleep latency (ß = 0.60; 95%CI: 0.49-0.82), fewer sleep disorders score in mothers (ß = 0.92; 95%CI: 0.85-0.99) and their infants (ß = 0.90; 95%CI: 0.84-0.96) as well as high mother's sleep efficiency (ß = 1.2; 95%CI: 1.1-1.31). CONCLUSIONS: According to our findings, adherence to DASH DP is associated with a lower score for sleep disorders in mothers and their infants.

Cell-free therapy based on stem cell-derived exosomes: A promising approach for wound healing.

There are several successive and overlapping phases in wound healing as a complex process. By the disruption of each of these phases, chronic non-healing wounds are resultant. Despite the present soothing surgeries, standard wound dressings and topical gels, the wound is often not completely closed. Today, stem cells have attracted a huge deal of attention therapeutically and pharmaceutically considering their unique features. However, they have some restrictions. Moreover, it is hoped to eliminate the limitations of cellular therapies based on their derivatives known as exosomes. Exosomes are extracellular vesicles secreted from cells. They have a diameter of almost 30-150 nm and miRNAs, mRNAs, and proteins that are possibly different from the source cell are included in exosomal contents. Such nanovesicles have a key role in the intercellular communication of pathological and physiological procedures. Exosome-based therapy is a new significant method for wound healing. By exosomes effects, wound management may be improved and a new therapeutic model may be highlighted for cell-free therapies with reduced side effects for the wound repair.

Menstrual problems in adolescence: relationship to serum vitamins A and E, and systemic inflammation.

BACKGROUND: Vitamin status and inflammatory mechanisms may be related to menstrual cycle abnormalities. We investigated the associations between serum fat soluble vitamin (vitamins A and E) concentrations and biomarkers of inflammation and antioxidant status with menstrual characteristics, primary dysmenorrhea (PD) and premenstrual syndrome (PMS) in healthy adolescents. METHODS: A total of 897 adolescent girls either suffering from PMS (n = 134), PD (n = 322), PMS and PD (n = 293) or healthy adolescents (n = 148) were recruited. Serum vitamin A and E, high-sensitivity C-reactive protein (hs-CRP), antibody titers to Hsp27 (anti-Hsp27), serum prooxidant-antioxidant balance (PAB), WBC, mean platelet volume (MPV), and platelet distribution width (PDW) and RBC distribution width (RDW) were measured. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and RDW-to-platelet ratio (RPR) were calculated. RESULTS: Girls with long bleeding periods had lower concentrations of serum vitamin E compared to those who reported a normal period duration. There were significantly differences between the groups reporting oligomenorrhea, regular menses and polymenorrhea with respect to NLR, RPR, MPV and PDW. Logistic regression demonstrated that the presence of both PMS and PD was positively related to higher serum hs-CRP, PAB and NLR, while serum vitamin A level was inversely related to the presence of PMS. CONCLUSIONS: We found that serum vitamin A, hs-CRP, PAB and NLR are significantly associated with the presence of PMS and PD. Inflammatory processes may contribute to the etiology, symptoms and severity of menstrual disorders. Prospective studies are needed to elucidate the possibility of targeting oxidative stress and inflammatory process for the amelioration of menstrual symptoms.

Therapeutic Effects of Aqueous Extracts of Cerasus Avium Stem on Ethylene Glycol- Induced Kidney Calculi in Rats.

PURPOSE: To investigate the therapeutic effects of the aqueous extract of Cerasus Avium stem on kidney calculi. MATERIALS AND METHODS: In this experimental study, forty-eight (48) male Wistar rats were randomly allocated into six (6) groups and were studied during a 30 day period. Group A served as normal control and Group B received 1% ethylene glycol in drinking water (EG group). C, D, E, and F Groups, received 1% ethylene glycol from day 1 and were used as prevention and treatment subjects. Rats in prevention groups of low dose (C) and high dose (D) extract, were gavaged with 200 and 400 mg/kg extract respectively from first day of the experiment and treatmentgroups of low dose (E) and high dose (F) extract, were gavaged with 200 and 400 mg/kg extract respectively from the 15th day of the experiment. RESULTS: On the 30th days of the experiment, serum level of magnesium and potassium decreased significantly in EG group compared with A,C,D,E and F groups (P < .05), while serum level of calcium, creatinine, uric acid, sodium and urine level of calcium, creatinine, uric acid, increased significantly in EG group compared with A,C,D,E and F groups (P < .05). In the prevention and treatment groups, the number of deposits decreased significantly compared with EG group on the 30th day (P < .05). CONCLUSION: Cerasus Avium stem has a therapeutic effect on calcium oxalate stones in rats with nephrolithiasis and reduces the number of calcium oxalate deposits.