Biomedical reports最新文献

Honey is a natural product derived from the insect Apis mellifera. Approximately 200 different compounds are included, making it a complex mixture with antimicrobial, antioxidant, and antidiabetic activity. Flavonoids and phenolic acids contained in honey are associated with its antioxidant capacity via mechanisms such as hydrogen donation and metallic ion chelation, although the exact antioxidant mechanism remains unknown. The aim of the present study was to: i) Estimate the antioxidant activity of a natural honey-based gel, commercially available under the trade name of 'Bear Strength honey gel' and to ii) assess the physiological and redox adjustments obtained after its consumption in healthy adult participants. For this purpose, 20 healthy participants (10 men and 10 women) included in their habitual diet 70 g of the honey-based gel for 14 days in a row. Pre- and post-consumption, physiological [weight, height, body mass index, body fat, waist-to-hip ratio, resting heart rate and blood pressure (BP)] and hematological (complete blood count) data were evaluated, along with the levels of five redox biomarkers: Glutathione (GSH), catalase (CAT), total antioxidant capacity (TAC), protein carbonyls (PCARBS) and thiobarbituric reactive substances (TBARS). The results revealed that the honey-based gel decreased the diastolic and mean arterial BP, especially in women, without affecting the rest of the physiological and hematological variables. Regarding the changes observed in antioxidant status variables, GSH was increased both in the total and women's group, while TAC was increased in all groups post-consumption. No changes were detected in the levels of CAT. Regarding oxidative stress, a decrease in the levels of TBARS in the total and women's group, was observed. PCARBS levels were decreased post-consumption only in the women's group. In conclusion, the present study demonstrated the potential positive effects of a honey-based gel on BP and redox status of healthy adults in a sex-specific manner.

Tyrosine kinase inhibitors are a clinically standard treatment option for non-small cell lung cancers (NSCLCs), the leading cause of cancer-related deaths in the US. These targeted agents include first, second and third generation tyrosine kinase inhibitors; however, these lack clinical efficacy in the treatment of NSCLC due to intrinsic and acquired resistance. This resistance may be a result of genetic aberrations in oncogenic signaling mediators of divergent pathways. The present study aimed to investigate a novel dual tyrosine kinase and PI3K inhibitor, PP121, as a targeted agent in NSCLC cell lines. The present study co-cultured PP121 with healthy human astrocytes, a prevalent cell type located in the brain of NSCLC brain metastases. To date, few preclinical studies have examined the efficacy of PP121 as an anticancer agent, and to the best of my knowledge, no previous studies have previously evaluated its therapeutic potential in the treatment of NSCLC. To investigate the clinical heterogeneity of NSCLC, patient-derived adenocarcinoma (ADC) and squamous cell carcinoma (SCC) xenograft models were used, which exhibited epidermal growth factor receptor (EGFR) mutations and mesenchymal-epithelial transition (MET) factor amplifications. Notably, both EGFR and MET are known contributors to tyrosine kinase inhibitor resistance; thus, the aforementioned mutations and amplifications enabled the effects of PP121 to be evaluated in these solid tumors. In addition, a co-cultured model system using both NSCLC cells and astrocytes was employed to assess the effects of PP121 on the invasion of ADC and SCC cells in a multicellular environment. Results of the present study demonstrated that PP121 exerted an antitumorigenic effect in the aforementioned model systems via downregulation of pharmacodynamic targets.

The multiple endocrine neoplasia type 1 gene coding the protein menin was originally identified in patients with multiple endocrine tumors, and is mainly expressed in the cell nucleus. Multiple lines of evidence have indicated that menin acts as a tumor suppressor protein interacting with other various proteins. The mechanism of menin inhibiting tumorigenesis remains unclear. The present study analyzed the expression of menin and IQ motif-containing GTPase-activating protein 1 (IQGAP1) proteins in gastric cancer tissues and cell lines, and investigated the association between these two molecules. Western blotting was used to determine the quantity of target proteins. Cell proliferation was measured using MTT assay. It was found that the protein expression of menin was lower in gastric cancer tissues and AGS cells, while the protein expression of IQGAP1 was higher, compared with the levels observed in normal tissues and GES-1 cells. Ectopic expression of IQGAP1 stimulated the proliferation of gastric cancer cells, but did not affect the expression of menin. However, overexpression of menin inhibited the proliferation of gastric cancer cells. The inhibition was partly achieved through inhibiting the expression of IQGAP1, which was accompanied by inhibition of PI3K and NF-κB expression. Taken together, the present results suggest a novel function for menin and IQGAP1 contributing to suppress the proliferation of gastric cancer cells.

The present study aimed to investigate the effects of combined Phyllanthus emblica Linn. (PE) and simvastatin (SIM) on diabetic wounds in male BALB/C mice. Bilateral full thickness wound excisions were performed in the control and diabetic groups (45 mg/kg streptozotocin, intraperitoneally injected daily for 5 days). The diabetic mice received daily treatment with four different types of cream: Vehicle [diabetes mellitus (DM) + Vehicle group], 100% PE (DM + PE group), 5% SIM (DM + SIM group) and combined 100% PE + 5% SIM (DM + Combination group) for 4, 7 and 14 days. The tissue malondialdehyde (MDA) and IL-6 protein levels, the number of infiltrated neutrophils, and the percentages of wound closure (%WC), capillary vascularity (%CV) and re-epithelialization (%RE) were subsequently measured. The results indicated that in the DM + Combination group, %CV and %WC were significantly increased when compared with the DM + Vehicle group on days 7 and 14. The tissue MDA content on day 14, and the number of infiltrated neutrophils on days 4 and 7 were significantly reduced in the DM + Combination group compared with those in the DM + Vehicle group. Furthermore, a strong positive correlation was revealed between %CV and %WC in the five groups on day 7 (r=0.736; P=0.0003). These findings indicated that topical application of combined PE and SIM could enhance wound healing by upregulating angiogenesis and reducing neutrophil infiltration in mice with diabetic wounds.

Pneumonia is one of the most prevalent infections in the intensive care unit (ICU), where pneumonia may occur during hospitalization in the ICU as a complication. ICU patients with central nervous system (CNS) injuries are not an exception, and they may even be more susceptible to infections such as pneumonia due to issues such as swallowing difficulties, the requirement for mechanical ventilation, and extended hospital stay. Numerous common CNS injuries, such as ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and intracerebral hemorrhage, can prolong hospital stay and increase the risk of pneumonia. Multidrug-resistant (MDR) microorganisms are a common and significant concern, with increased mortality in nosocomial pneumonia. However, research on pneumonia due to MDR pathogens in patients with CNS injuries is limited. The aim of the present review was to provide the current evidence regarding pneumonia due to MDR pathogens in patients with CNS injuries. The prevalence of pneumonia due to MDR pathogens in CNS injuries differs among different settings, types of CNS injuries, geographical areas, and time periods in which the studies were performed. Specific risk factors for the emergence of pneumonia due to MDR pathogens have been identified in ICUs and neurological rehabilitation units. Antimicrobial resistance is currently a global issue, although using preventive measures, early diagnosis, and close monitoring of MDR strains may lessen its impact. Since there is a lack of information on these topics, more multicenter prospective studies are required to offer insights into the clinical features and outcomes of these patients.

Radioresistant cancer cells lead to poor prognosis after radiotherapy. However, the mechanisms underlying cancer cell radioresistance have not been fully elucidated. Thus, the DNA damage response of clinically relevant radioresistant oral squamous cell carcinoma HSC2-R cells, established by long-term exposure of parental HSC2 cells to fractionated radiation, was investigated. The DNA double-strand break (DSB) repair protein-specific inhibitor, NU7441, which targets DNA-dependent protein kinase catalytic subunit (DNA-PKcs) phosphorylation, and IBR2, which targets Rad51, were administered to HSC2 and HSC2-R cells. NU7441 administration eliminated colony formation in both cell lines under 6 Gy X-ray irradiation, whereas IBR2 did not affect colony formation. NU7441 and IBR2 significantly enhanced 6 Gy X-ray irradiation-induced apoptosis in HSC2-R cells. In HSC2-R cells, cell cycle arrest released earlier than in HSC2 cells, and phosphorylated-H2A histone family member X (γH2AX) expression rapidly decreased. Following NU7441 administration, γH2AX expression and the cell percentages of the G2/M phase were not decreased at 48 h after treatment in HSC2-R cells. DNA-PKcs has been demonstrated to regulate non-homologous end-joining (NHEJ) and homologous recombination (HR) repair, and the later phase of DSB repair is dominated by HR. Therefore, the results of the present study indicated that the DSB repair mechanism in HSC2-R cells strongly depends on NHEJ and loss of HR repair function. The present study revealed a potential mechanism underlying the acquired radioresistance and therapeutic targets in radioresistant cancer cells.

The present study aimed to investigate the dynamic changes in peripheral blood leucocyte subpopulations, cytokine and miRNA levels, and changes in computed tomography (CT) scores in patients with severe coronavirus disease 2019 (COVID-19) (n=14) and age-matched non-COVID-19 volunteers (n=17), which were included as a reference control group. All data were collected on the day of patient admission (day 0) and on the 7th, 14th and 28th days of follow-up while CT of the lungs was performed on weeks 2, 8, 24 and 48. On day 0, lymphopenia and leucopenia were detected in most patients with COVID-19, as well as an increase in the percentage of banded neutrophils, B cells, and CD4⁺ Treg cells, and a decrease in the content of PD-1^low T cells, classical, plasmacytoid, and regulatory dendritic cells. On day 7, the percentage of T and natural killer cells decreased with a concurrent increase in B cells, but returned to the initial level after treatment discharge. The content of different T and dendritic cell subsets among CD45⁺ cells increased during two weeks and remained elevated, suggesting the activation of an adaptive immune response. The increase of PD-1-positive subpopulations of T and non-T cells and regulatory CD4 T cells in patients with COVID-19 during the observation period suggests the development of an inflammation control mechanism. The levels of interferon γ-induced protein 10 (IP-10), tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 decreased on day 7, but increased again on days 14 and 28. C-reactive protein and granulocyte colony-stimulating factor (G-CSF) levels decreased gradually throughout the observation period. The relative expression levels of microRNA (miR)-21-5p, miR-221-3p, miR-27a-3p, miR-146a-5p, miR-133a-3p, and miR-126-3p were significantly higher at the beginning of hospitalization compared to non-COVID-19 volunteers. The plasma levels of all miRs, except for miR-126-3p, normalized within one week of treatment. At week 48, CT scores were most prominently correlated with the content of lymphocytes, senescent memory T cells, CD127⁺ T cells and CD57⁺ T cells, and increased concentrations of G-CSF, IP-10, and macrophage inflammatory protein-1α.

Chronic stress has been recognized to induce the alterations of neuronal and glial cells in the hippocampus, and is thus implicated in cognitive dysfunction. There is increasing evidence to indicate that natural compounds capable of exerting neuroprotective and antioxidant activities, may function as potential therapeutic agents for cognitive impairment. The present study examined the neuroprotective effects of pinostrobin from Boesenbergia rotunda (L.) against chronic restraint stress (CRS)-induced cognitive impairment associated with the alterations of oxidative stress, neuronal density and glial fibrillary acidic protein (GFAP) of astrocytes in the hippocampus. For this purpose, male Wistar rats were administered once daily with pinostrobin (20 and 40 mg/kg, per os) prior to exposure to CRS (6 h/day) for 21 days. The cognitive behaviors, the concentration of malondialdehyde, and the activities of superoxide dismutase and catalase were determined. Histologically, the alterations in astrocytic GFAP and excitatory amino acid transporter 2 (EAAT2) in the hippocampus were examined. The results revealed that pinostrobin potentially attenuated cognitive impairment in the Y-maze and in novel object recognition tests, with a reduction in oxidative stress. Furthermore, pinostrobin effectively increased neuronal density, as well as the immunoreactivities of GFAP and EAAT2 in the hippocampus. Taken together, these findings indicate that treatment with pinostrobin alleviates chronic stress-induced cognitive impairment by exerting antioxidant effects, reducing neuronal cell damage, and improving the function of astrocytic GFAP and EAAT2. Thus, pinostrobin may have potential for use as a neuroprotective agent to protect against chronic stress-induced brain dysfunction and cognitive deficits.

Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide. The poor specificity and sensitivity of the fecal occult blood test has prompted the development of CRC-related genetic markers for CRC screening and treatment. Gene expression profiles in stool specimens are effective, sensitive and clinically applicable. Herein, a novel advantage of using cells shed from the colon is presented for cost-effective CRC screening. Molecular panels were generated through a series of leave-one-out cross-validation and discriminant analyses. A logistic regression model following reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry was used to validate a specific panel for CRC prediction. The panel, consisting of ubiquitin-conjugating enzyme E2 N (UBE2N), inosine monophosphate dehydrogenase 1 (IMPDH1), dynein cytoplasmic 1 light intermediate chain 1 (DYNC1LI1) and phospholipase A and acyltransferase 2 (HRASLS2), accurately recognized patients with CRC and could thus be further investigated as a potential prognostic and predictive biomarker for CRC. UBE2N, IMPDH1 and DYNC1LI1 expression levels were upregulated and HRASLS2 expression was downregulated in CRC tissues. The predictive power of the panel was 96.6% [95% confidence interval (CI), 88.1-99.6%] sensitivity and 89.7% (95% CI, 72.6-97.8%) specificity at a predicted cut-off value at 0.540, suggesting that this four-gene panel testing of stool specimens can faithfully mirror the state of the colon. On the whole, the present study demonstrates that screening for CRC or cancer detection in stool specimens collected non-invasively does not require the inclusion of an excessive number of genes, and colonic defects can be identified via the detection of an aberrant protein in the mucosa or submucosa.