Senescence of bone marrow mesenchymal stem cells in Wistar male rats receiving normal chow/high-calorie diets with/without vitamin D.

Bone marrow mesenchymal stem cells (BM-MSCs) have a momentous function in the composition of the bone marrow microenvironment because of their many valuable properties and abilities, such as immunomodulation and hematopoiesis. The features and actions of MSCs are influenced by senescence, which may be affected by various factors such as nutritional/micronutrients status, e.g., vitamin D. This study aimed to examine the effects of a high-calorie diet (HCD) with/without vitamin D on BM-MSCs senescence. In the first phase, 48 middle-aged rats were fed a normal chow diet (NCD, n = 24) and an HCD (n = 24) for 26 weeks. Afterward, the rats in each group were randomly divided into three equal subgroups. Immediately, eight-rat from each diet group were sacrificed to assess the HCD effects on the first phase measurements. In the second phase, the remaining 4 groups of rats were fed either NCD or HCD with (6 IU/g) or without vitamin D (standard intake: 1 IU/g); in other words, in this phase, the animals were fed (a) NCD, (b) NCD plus vitamin D, (c) HCD, and (d) HCD plus vitamin D for 4 months. BM-MSCs were isolated and evaluated for P16INK4a, P38 MAPK, and Bmi-1 gene expression, reactive oxygen species (ROS) levels, SA-ß-gal activity, and cell cycle profile at the end of both phases. After 26 weeks (first phase), the ROS level, SA-ß-gal-positive cells, and cells in the G1 phase were significantly higher in HCD-fed rats than in NCD-fed ones (P < 0.05). HCD prescription did not significantly affect cells in the S and G2 phases (p > 0.05). Compared with the NCD-fed animals, P16INK4a and P38 MAPK gene expression were up-regulated in the HCD-fed animals; also, Bmi-1 gene expression was down-regulated (P < 0.05). BM-MSCs from vitamin D-treated rats (second phase) exhibited reduced mRNA levels of P16INK4a and P38 MAPK genes and increased Bmi-1 mRNA levels (all P < 0.05). Vitamin D prescription also declined the percentage of SA-ß-gal-positive cells, ROS levels, and the cells in the G1 phase and increased the cells in the S phase in both NCD and HCD-fed animals (P < 0.05). The reduction of the cells in the G2 phase in rats fed with an NCD plus vitamin D was statistically non-significant (P = 0.128) and significant in HCD plus vitamin D rats (P = 0.002). HCD accelerates BM-MSCs senescence, and vitamin D reduces BM-MSCs senescence biomarkers.

Corneal biomechanics in normal and subclinical keratoconus eyes.

BACKGROUND: The diagnosis of keratoconus, as the most prevalent corneal ectatic disorder, at the subclinical stage gained great attention due to the increased acceptance of refractive surgeries. This study aimed to assess the pattern of the corneal biomechanical properties derived from Corneal Visualization Scheimpflug Technology (Corvis ST) and evaluate the diagnostic value of these parameters in distinguishing subclinical keratoconus (SKC) from normal eyes. METHODS: This prospective study was conducted on 73 SKC and 69 normal eyes. Subclinical keratoconus eyes were defined as corneas with no clinical evidence of keratoconus and suspicious topographic and tomographic features. Following a complete ophthalmic examination, topographic and tomographic corneal assessment via Pentacam HR, and corneal biomechanical evaluation utilizing Corvis ST were done. RESULTS: Subclinical keratoconus eyes presented significantly higher Deformation Amplitude (DA) ratio, Tomographic Biomechanical Index (TBI), and Corvis Biomechanical Index (CBI) rates than the control group. Conversely, Ambrósio Relational Thickness to the Horizontal profile (ARTh), and Stiffness Parameter at the first Applanation (SPA1) showed significantly lower rates in SKC eyes. In diagnosing SKC from normal eyes, TBI (AUC: 0.858, Cut-off value: > 0.33, Youden index: 0.55), ARTh (AUC: 0.813, Cut-off value: ≤ 488.1, Youden index: 0.58), and CBI (AUC: 0.804, Cut-off value: > 0.47, Youden index: 0.49) appeared as good indicators. CONCLUSIONS: TBI, CBI, and ARTh parameters could be valuable in distinguishing SKC eyes from normal ones.

NLRP3 inflammasome: Its regulation and involvement in atherosclerosis.

Inflammasomes are intracellular complexes involved in the innate immunity that convert proIL-1ß and proIL-18 to mature forms and initiate pyroptosis via cleaving procaspase-1. The most well-known inflammasome is NLRP3. Several studies have indicated a decisive and important role of NLRP3 inflammasome, IL-1ß, IL-18, and pyroptosis in atherosclerosis. Modern hypotheses introduce atherosclerosis as an inflammatory/lipid-based disease and NLRP3 inflammasome has been considered as a link between lipid metabolism and inflammation because crystalline cholesterol and oxidized low-density lipoprotein (oxLDL) (two abundant components in atherosclerotic plaques) activate NLRP3 inflammasome. In addition, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and lysosome rupture, which are implicated in inflammasome activation, have been discussed as important events in atherosclerosis. In spite of these clues, some studies have reported that NLRP3 inflammasome has no significant effect in atherogenesis. Our review reveals that some molecules such as JNK-1 and ASK-1 (upstream regulators of inflammasome activation) can reduce atherosclerosis through inducing apoptosis in macrophages. Notably, NLRP3 inflammasome can also cause apoptosis in macrophages, suggesting that NLRP3 inflammasome may mediate JNK-induced apoptosis, and the apoptotic function of NLRP3 inflammasome may be a reason for the conflicting results reported. The present review shows that the role of NLRP3 in atherogenesis can be significant. Here, the molecular pathways of NLRP3 inflammasome activation and the implications of this activation in atherosclerosis are explained.

Falling and rising in the vortex of cancer: children's adaptation with cancer: a qualitative study.

BACKGROUND: Cancer is a considerable health problem worldwide and the second leading cause of death in children. It has many physical, psychological, and social consequences for children and their families. The ability to adapt to cancer plays a vital role in the recovery and quality of life of affected children. This study aimed to explain the adaptation of children with cancer to their disease. METHODS: This qualitative study adopted the directed content analysis approach based on the Roy nursing model. The participants were nine children with cancer aged 6-18 years old, five family members, four nurses, one doctor, one teacher, and two charity association members, recruited by purposive sampling method. The information was collected via individual semi-structured interviews, a focus group discussion, and field notes. The data were analyzed simultaneously with data collection using the Elo and Kyngäs method. The study rigor was ensured based on the Guba and Lincoln criteria. FINDINGS: Of the four categories of physical challenges, fragile self-concept, the difficulty of role transition, and disruption of the path to independence, the theme of Falling and rising in the cancer vortex was abstracted. CONCLUSION: Based on the Roy model, the children in the present study were at the compensatory level of adaptation. This research demonstrates that the adaptation of children being treated for cancer is fragile and not constant. With each hospitalization and exacerbation of the disease, they made efforts to adapt to their disease using regulatory and cognitive subsystems. Paying attention to different stimulants and the effects of support systems on physical challenges, fragile self-concept, difficult role transition, and disruption of the path to independence for each child, as well as providing individualized care for these children, can help their adaptation to and healthy transition from the vortex of cancer. The Roy adaptation model was helpful and efficient for elucidating the adaptation of children with cancer. Providing care for children by healthcare specialists, especially nurses, should be theory-based and individualized.

Protective Effect of Vitamin D Supplementation on Some Hemogram Derived Inflammatory Indices in Normal and High-Fat Diet Fed Male Wistar Rats.

Background: Hematological inflammatory indices are currently suggested to assess systemic inflammation. This study aims to investigate a vitamin D supplementation effect on hematological indices of inflammation in rats. Method: Forty-eight middle-aged male rats were allocated into a normal diet (ND) group (10% fat) and a high-fat diet (HFD) group (60% fat). The animals were fed for 26 weeks. After this period, each group was randomly divided into three subgroups, each of 8 rats: Group (1): animals were fed the ND and HFD containing 1 IU/g vitamin D for 4 months, group (2): animals were fed the ND and HFD containing 6 IU/g vitamin D for 4 months and group (3): animals were euthanized to evaluate the HFD effect. Serum 25-hydroxyvitamin D level, white blood cell count (WBCs), platelet count, platelet crit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) were measured. Results: The HFD, significantly increased body weight, PCT, PDW, PLR, NLR, and MLR and significantly reduced serum vitamin D levels compared to the ND (P < 0.05). There was a significant decrease in food intake, MPV, PDW, and NLR after vitamin D supplementation in the ND-fed group (P < 0.05). A significant reduction in platelet count, PCT, and MLR was observed after vitamin D supplementation in HFD-fed rats (P < 0.05). Conclusions: In our study, some hemogram-derived inflammatory indices were higher in the HFD-fed group, and vitamin D supplementation lowering effects on some hematological indices were seen in both ND and HFD groups.

Short Communication: Prevalence of Listeria monocytogenes in Raw Milk of Healthy Sheep and Goats.

Listeria monocytogenes, one of the most important bacterial pathogens transmitted through milk, causes listeriosis in humans and animals. This study aimed to investigate the prevalence of L. monocytogenes in raw milk of healthy sheep and goats in the west of Iran (Lorestan Province) by touchdown PCR (TD-PCR). Listeria spp. were found in milk samples taken from 21 sheep (29.16%) and 3 goats (10.71%) whereas L. monocytogenes was isolated from milk samples taken from 4 sheep (5.55%) and 1 goat (3.75%). The results showed that there was a significant difference between sheep and goats in the prevalence of Listeria spp. in their raw milk (p < 0.05), but no significant difference was observed between them in the prevalence of L. monocytogenes. The study findings suggested that the raw milk of healthy sheep and goats was infected with L. monocytogenes and warned of the risk of human infection with listeriosis following consumption of raw and unpasteurized milk.

Impacts of COVID-19 Pandemic on Micro and Small Enterprises: Evidence From Rural Areas of Iran.

Since 2020, the outbreak of the COVID-19 crisis has caused a great deal of social and economic damages to micro and small-scale enterprises (MSEs). This research examined the most common damages of this crisis in active and inactive rural MSEs and also assessed different kind of responses the managers and owners of theses MSEs have received dealing with these damages. The sample population of this study consisted of all managers of 72 active and 38 closed rural MSEs in the Dastjerd village, Hamedan, Iran. These MSEs were mainly garment small factories. This research utilized a mixed approach (quantitative-qualitative) to study the research objectives in depth. First, in qualitative part, semi-constructed interviews and field visits were done. Then, using quantitative, results of the qualitative section, previous studies and the existing literature, a researcher-made questionnaire was created. Based on qualitative part information through interviews, damages of rural MSEs during COVID-19 pandemic were categorized into three classes, including damages related to production, and financial and marketing issues. Also, two categories of managers' responses that could be labeled as passive and adaptive behavior were identified. Findings showed that active rural MSEs have taken more adaptive measures and tried to find appropriate ways to reduce or overcome damages. Active MSEs were mainly owned and managed collaboratively by more literate and experienced managers. Also results revealed that rural MSEs' managers reacted to different kinds of damages based on their ability, knowledge, and experience. Based on research results, managers' knowledge and skills can help them find more adaptive solutions to keep the firms stable and overcome damages. It can be concluded that COVID-19 pandemic has a great impact on rural MSEs and they need more financial support and managerial advice to overcome this kind of crisis situation.

Potential of Lactobacillus acidophilus to modulate cytokine production by peripheral blood monocytes in patients with endometriosis.

Background and Objectives: Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. Peripheral blood monocytes cells (PBMCs) may have altered function to some extent in women with endometriosis. Lactobacillus acidophilus is a probiotic bacterium within the human body with the ability of alleviating many inflammatory diseases. Here, we examined the effect of L. acidophilus on PBMCs of endometriosis patients. Materials and Methods: In this study, peripheral blood samples were obtained from endometriosis patients (n=11) and non-endometriosis individuals (n=11). After isolation of peripheral blood mononuclear cells with Ficoll, cells were cultured in the presence and absence of phytohemagglutinin. Also, these cells were co-cultured with 1×106 CFU/ml of L. acidophilus. IL-6 and IL-1 cytokines were measured by ELISA method and the two groups were evaluated and compared. Results: The results showed that in endometriosis patients, the production of pro-inflammatory cytokines, including IL-1 and IL-6, by PBMC was increased compared to non-endometriosis subjects, and stimuli such as PHA intensified this elevation. Also, L. acidophilus increased the levels of pro-inflammatory cytokines including IL-1 and IL-6. However, the production of these cytokines decreased due to the modulatory properties of bacterial cells after 48 h. Conclusion: According to the results of the current study, IL-1 and IL-6 production was significantly increased in PMBCs of endometriosis patients compared to that of the healthy controls. Also, Lactobacillus acidophilus was considered as an antigenic compound and induced IL-1 and IL-6 production. According to these results, probiotics can be further used for the treatment of endometriosis patients and more investigations are needed to confirm these results.