| 1. |
- Alehagen, Urban, 1951-, et al.
(författare)
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Genetic variance and plasma concentration of CD93 is associated with cardiovascular mortality : Results from a 6.7-year follow-up of a healthy community-living elderly population
- 2020
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 22:6, s. 4629-4636
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation is one of the fundamental processes in numerous diseases. Cluster of differentiation (CD) 93, a glycoprotein, has been reported to be associated with a number of these diseases. There are reports indicating that a high plasma level of CD93 is associated with adverse events in ischaemic heart disease. Additionally, there are reports indicating different cardiovascular risks between different single nucleotide polymorphisms (SNPs) of CD93. Therefore, the present study aimed to determine whether the plasma concentration of CD93 and polymorphism of rs2749812 in CD93 were associated with clinical conditions and mortality in an elderly population. In 470 healthy elderly community-living individuals a novel clinical examination involving echocardiography and blood sampling was performed. The population was followed for 6.7 years. Plasma levels of CD93 and SNP analyses of rs2749812 of CD93 using PCR methodology were used. During the follow-up period, 106 (22.6%) all-cause and 61 (13.0%) cardiovascular deaths were registered. Those with the highest plasma concentration had markedly higher all-cause mortality. Evaluating the A/A, A/G and G/G genotypes, the G/G group exhibited significantly higher cardiovascular mortality (P=0.026), and an almost two-fold increased risk in a multivariate Cox regression model compared with the A/G genotype. Evaluation of subgroups with respect to sex, diabetes and hypertension revealed markedly increased cardiovascular risk in the G/G genotype in all subgroups. All results persisted in the multiple models used. In the present study, the glycoprotein CD93 was demonstrated to have prognostic cardiovascular information, with increased risk for those with a high plasma concentration. Furthermore, the G/G genotype of rs2749812 of CD93 has a significantly higher cardiovascular risk, as demonstrated here, and could therefore be regarded as a possible cardiovascular risk biomarker that might in the future be used to offer optimised cardiovascular patient handling. However, this was a small study, and more research is required.
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| 2. |
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| 3. |
- Fragkiadaki, Persefoni, et al.
(författare)
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Telomerase inhibitors and activators in aging and cancer : A systematic review
- 2022
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 25:5
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Forskningsöversikt (refereegranskat)abstract
- The main aim of the present systematic review was to summarize the most frequently used telomerase regulators with an impact on aging and cancer that are referred to in in vitro and in vivo studies. For this purpose, a systematic review of the available literature on telomerase regulators referred to in articles from PubMed and Scopus libraries published from 2002 to 2021 and in accordance with PRISMA 2020 criteria, was conducted. Articles were included if they met the following criteria: They referred to telomerase modulators in aging and in cancer and were in vitro and/or in vivo studies, while studies that did not provide sufficient data or studies not written in English were excluded. In the present systematic review, 54 publications were included, of which 29 were full-text published studies, 11 were full-text reviews, 10 structure-based design studies and 4 abstracts are reported in this review. Telomerase regulators were then categorized as synthetic direct telomerase inhibitors, synthetic indirect telomerase inhibitors, synthetic telomerase activators, natural direct telomerase activators, natural telomerase inhibitors and natural indirect telomerase activators, according to their origin and their activity. On the whole, as demonstrated herein, telomerase regulators appear to be promising treatment agents in various age-related diseases. However, further in vivo and in vitro studies need to be performed in order to clarify the potentiality of telomerase as a therapeutic target.
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| 4. |
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| 5. |
- Ohlsson, Bodil
(författare)
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Functional bowel symptoms in the general population (Review)
- 2022
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 26:1
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Forskningsöversikt (refereegranskat)abstract
- Several patients with irritable bowel syndrome (IBS) do not seek medical attention for their symptoms. When patients with IBS seek help, the majority of them are handled at primary healthcare centers, whereas research studies are performed at tertiary healthcare centers. The present study aimed to summarize findings from >4,000 participants of the general population included in the Malmö Offspring Study (inclusion rate 46.7%). The participants were clinically examined, their blood and fecal samples collected, and their questionnaires completed. The participants were divided into subjects with or without self?reported IBS and those having functional gastrointestinal (GI) symptoms in the past 2 weeks. The presence of IBS and GI symptoms in the participants were associated with each other. Zonulin levels did not differ between participants with or without GI diseases and were not associated with the degree of GI symptoms. The parameters low body weight at birth and small for gestational age were associated with the degree of the symptoms' influence on daily life. IBS and GI symptoms were positively associated with Blautia abundance. Beta?diversity differed between participants with or without these two conditions. Positive correlations were noted between the degree of diarrhea and the mean 24?h measurements of systolic blood pressure, diastolic blood pressure, and heart rate. Both IBS and GI symptoms were associated with female sex, smoking, stress, poor sleeping habits, unemployment, drug use, and a family history of GI diseases, whereas younger age was inversely associated with IBS and its associated symptoms. In conclusion, only a limited number of medical findings could be identified in participants with IBS and GI symptoms, whereas sociodemographic and environmental conditions were associated with these entities.
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| 6. |
- Ohlsson, Bodil
(författare)
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Theories behind the effect of starch‑ and sucrose‑reduced diets on gastrointestinal symptoms in irritable bowel syndrome (Review)
- 2021
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 24:4
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Forskningsöversikt (refereegranskat)abstract
- increased amounts of starch and sugar have been added to the diet in the Western world during the last decades. undigested carbohydrates lead to bacterial fermentation and gas production with diffusion of water, causing abdominal bloating, pain and diarrhea. Therefore, dietary advice is the first line of treatment of irritable bowel syndrome (IBS), a disease characterized by abdominal pain and altered bowel habits without any organic findings. recently, a diet with a reduction of starch and sucrose led to a marked effect on gastrointestinal (GI) symptoms. The mechanism is unknown, but three possible mechanisms are presented in the present review. First, functional variants of the enzyme sucrase‑isomaltase (SI) have been described in IBS. A subgroup of patients with IBS may thus suffer from partial SI deficiency with reduced digestion of starch and sucrose. Second, fructose absorption is less efficient than glucose absorption, which may lead to a physiological fructose malabsorption when ingesting high amounts of sucrose. a third mechanism is that high‑sugar diets causing hypergly‑ cemia, hyperinsulinemia and weight gain have led to painful neuropathy in animal models; whereas, improved metabolic control in humans has led to improvement of neuropathy. Starch‑ and sucrose‑reduced diets lead to decreased levels of c‑peptide, insulin, gastric inhibitory peptide, leptin and weight reduction. These metabolic changes may reduce the excitability of the hypersensitive nervous system often found in IBS and, thereby, lead to the reduced symptoms found after the diet. in conclusion, further studies are needed to investi‑ gate the pathophysiology behind development of symptoms after starch and sucrose intake, and the mechanisms behind symptom relief after reduced intake.
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| 8. |
- Shi, Yuanping, et al.
(författare)
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Increased expression levels of inflammatory cytokines and adhesion molecules in lipopolysaccharide‑induced acute inflammatory apoM‑/‑ mice
- 2020
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 22:4, s. 3117-3126
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Tidskriftsartikel (refereegranskat)abstract
- apolipoproteinM(apoM)mayserveaprotectiverole inthedevelopmentofinflammation.Nuclearfactor‑κB(nF-κB) and its downstream factors (including a number of inflammatory cytokines and adhesion molecules) are essential for the regulation of inflammatory processes. In the present study, the importance of apoM in lipopolysaccharide (LPS)‑induced acute inflammation and its potential underlying mechanisms, were investigated using an apoM‑knockout mouse model. The levels of inducible nitric oxide synthase (iNOS), NF‑κB, interleukin (IL)‑1β, intercellular adhesion molecule 1 (ICAM‑1) and vascular cell adhesion protein 1 (VCAM‑1) were detected using reverse transcription‑quantitative PCR and western blotting. The serum levels of IL‑6 and IL‑10 were detected using Luminex technology. The results demonstrated that the protein levels of inoS, nF-κB, il-1β, ICAM‑1 and VCAM‑1 were significantly increased in apoM-/- mice compared with those in apoM+/+ mice. In addition, two‑way ANOVA revealed that the interaction between apoM and LPS had a statistically significant effect on a number of factors, including the mRNA expression levels of hepatic iNOS, NF‑κB, il-1β, icaM-1 and VCAM‑1. Notably, the effects of apoM and 10 mg/kg LPS on the levels of IL‑6 and IL‑10 were the opposite of those induced by 5 mg/kg LPS, which could be associated with the dual anti‑ and pro‑inflammatory effects of IL‑6 and IL‑10. Collectively, the results of the present study revealed that apoM is an important regulator of inflammatory cytokine and adhesion molecule production in LPS‑induced inflammation, which may consequently be associated with the severity of inflammation. These findings indicated that the anti‑inflammatory effects of apoM may partly result from the inhibition of the nF-κB pathway.
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| 9. |
- Vazquez-Sanchez, Ernesto A., et al.
(författare)
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Heptapeptide HP3 acts as a potent inhibitor of experimental imiquimod-induced murine psoriasis and impedes the trans-endothelial migration of mononuclear cells
- 2020
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Ingår i: Molecular Medicine Reports. - : SPANDIDOS PUBL LTD. - 1791-2997 .- 1791-3004. ; 22:1, s. 507-515
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Tidskriftsartikel (refereegranskat)abstract
- During the progression of psoriatic lesions, abundant cellular infiltration of myeloid cells, such as macrophages and activated dendritic cells, occurs in the skin and the infiltrating cells interact with naive lymphoid cells to generate a T helper (Th)1 and Th17 environment. Therapies to treat psoriasis include phototherapy, non-steroidal and steroidal drugs, as well as antibodies to block tumor necrosis factor-alpha, interleukin (IL)-17-A and IL-12/IL-23, which all focus on decreasing the proinflammatory hallmark of psoriasis. The present study obtained the heptapeptide HP3 derived from phage display technology that blocks mononuclear cell adhesion to endothelial cells and inhibits trans-endothelial migrationin vitro. The activity of the heptapeptide in a murine model of psoriasis was also assessed, which indicated that early administration inhibited the development of psoriatic lesions. Therefore, the results suggested that HP3 may serve as a potential therapeutic target for psoriasis.
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| 10. |
- Zhu, Ziqiang, et al.
(författare)
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Integrative microRNA and mRNA expression profiling in acute aristolochic acid nephropathy in mice
- 2020
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 22:4, s. 3367-3377
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Tidskriftsartikel (refereegranskat)abstract
- In acute aristolochic acid nephropathy (AAN), aristolochic acid (AA) induces renal injury and tubulointerstitial fibrosis. However, the roles of microRNAs (miRNAs/miRs) and mRNAs involved in AAN are not clearly understood. The aim of the present study was to examine AA-induced genome-wide differentially expressed (DE) miRNAs and DE mRNAs using deep sequencing in mouse kidneys, and to analyze their regulatory networks. In the present self-controlled study, mice were treated with 5 mg/kg/day AA for 5 days, following unilateral nephrectomy. AA-induced renal injury and tubulointerstitial fibrosis were detected using hematoxylin and eosin staining and Masson's trichrome staining in the mouse kidneys. A total of 82 DE miRNAs and 4,605 DE mRNAs were identified between the AA-treated group and the self-control group. Of these DE miRNAs and mRNAs, some were validated using reverse transcription-quantitative PCR. Expression levels of the profibrotic miR-21, miR-433 and miR-132 families were significantly increased, whereas expression levels of the anti-fibrotic miR-122-5p and let-7a-1-3p were significantly decreased. Functions and signaling pathways associated with the DE miRNAs and mRNAs were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 767 DE pairs (in opposing directions) of miRNAs and their mRNA targets were identified. Among these, regulatory networks of miRNAs and mRNAs were analyzed using KEGG to identify enriched signaling pathways and extracellular matrix-associated pathways. In conclusion, the present study identified genome-wide DE miRNAs and mRNAs in the kidneys of AA-treated mice, as well as their regulatory pairs and signaling networks. The present results may improve the understanding of the role of DE miRNAs and their mRNA targets in the pathophysiology of acute AAN.
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