Articles from MDPI


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  • Santos, Joao; Heiniö, Camilla; Quixabeira, Dafne; Zafar, Sadia; Clubb, James; Pakola, Santeri; Cervera-Carrascon, Victor; Havunen, Riikka; Kanerva, Anna; Hemminki, Akseli (Multidisciplinary Digital Publishing Institute, 2021)
    Immunotherapy with tumor-infiltrating lymphocytes (TIL) or oncolytic adenoviruses, have shown promising results in cancer treatment, when used as separate therapies. When used in combination, the antitumor effect is synergistically potentiated due oncolytic adenovirus infection and its immune stimulating effects on T cells. Indeed, studies in hamsters have shown a 100% complete response rate when animals were treated with oncolytic adenovirus coding for TNFa and IL-2 (Ad5/3-E2F-D24-hTNFa-IRES-hIL2; TILT-123) and TIL therapy. In humans, one caveat with oncolytic virus therapy is that intratumoral injection has been traditionally preferred over systemic administration, for achieving sufficient virus concentrations in tumors, especially when neutralizing antibodies emerge. We have previously shown that 5/3 chimeric oncolytic adenovirus can bind to human lymphocytes for avoidance of neutralization. In this study, we hypothesized that incubation of oncolytic adenovirus (TILT-123) with TILs prior to systemic injection would allow delivery of virus to tumors. This approach would deliver both components in one self-amplifying product. TILs would help deliver TILT-123, whose replication will recruit more TILs and increase their cytotoxicity. In vitro, TILT-123 was seen binding efficiently to lymphocytes, supporting the idea of dual administration. We show in vivo in different models that virus could be delivered to tumors with TILs as carriers.
  • Benedict, Christian; Brandão, Luiz Eduardo Mateus; Merikanto, Ilona; Partinen, Markku; Bjorvatn, Bjørn; Cedernaes, Jonathan (Multidisciplinary Digital Publishing Institute, 2021)
    The COVID-19 pandemic and related restrictions, such as stay-at-home-orders, have significantly altered daily routines and lifestyles. Given their importance for metabolic health, we herein compared sleep and meal timing parameters during vs. before the COVID-19 pandemic based on subjective recall, in an anonymous Swedish survey. Among 191 adults (mean age: 47 years; 77.5% females), we show that social jetlag, i.e., the mismatch in sleep midpoint between work and free days, was reduced by about 17 min during the pandemic compared with the pre-pandemic state (<i>p</i> &lt; 0.001). Concomitantly, respondents’ sleep midpoint was shifted toward morning hours during workdays (<i>p</i> &lt; 0.001). A later daily eating midpoint accompanied the shift in sleep timing (<i>p</i> = 0.001). This effect was mainly driven by a later scheduled first meal (<i>p</i> &lt; 0.001). No difference in the timing of the day’s last meal was found (<i>p</i> = 0.814). Although our survey was limited in terms of sample size and by being cross-sectional, our results suggest that the delay in sleep timing due to the COVID-19 pandemic was accompanied by a corresponding shift in the timing of early but not late meals.
  • Gedefaw, Melakeneh G.; Geli, Hatim M. E.; Abera, Temesgen Alemayehu (Multidisciplinary Digital Publishing Institute, 2021)
    Rangelands provide significant socioeconomic and environmental benefits to humans. However, climate variability and anthropogenic drivers can negatively impact rangeland productivity. The main goal of this study was to investigate structural and productivity changes in rangeland ecosystems in New Mexico (NM), in the southwestern United States of America during the 1984–2015 period. This goal was achieved by applying the time series segmented residual trend analysis (TSS-RESTREND) method, using datasets of the normalized difference vegetation index (NDVI) from the Global Inventory Modeling and Mapping Studies and precipitation from Parameter elevation Regressions on Independent Slopes Model (PRISM), and developing an assessment framework. The results indicated that about 17.6% and 12.8% of NM experienced a decrease and an increase in productivity, respectively. More than half of the state (55.6%) had insignificant change productivity, 10.8% was classified as indeterminant, and 3.2% was considered as agriculture. A decrease in productivity was observed in 2.2%, 4.5%, and 1.7% of NM’s grassland, shrubland, and ever green forest land cover classes, respectively. Significant decrease in productivity was observed in the northeastern and southeastern quadrants of NM while significant increase was observed in northwestern, southwestern, and a small portion of the southeastern quadrants. The timing of detected breakpoints coincided with some of NM’s drought events as indicated by the self-calibrated Palmar Drought Severity Index as their number increased since 2000s following a similar increase in drought severity. Some breakpoints were concurrent with some fire events. The combination of these two types of disturbances can partly explain the emergence of breakpoints with degradation in productivity. Using the breakpoint assessment framework developed in this study, the observed degradation based on the TSS-RESTREND showed only 55% agreement with the Rangeland Productivity Monitoring Service (RPMS) data. There was an agreement between the TSS-RESTREND and RPMS on the occurrence of significant degradation in productivity over the grasslands and shrublands within the Arizona/NM Tablelands and in the Chihuahua Desert ecoregions, respectively. This assessment of NM’s vegetation productivity is critical to support the decision-making process for rangeland management; address challenges related to the sustainability of forage supply and livestock production; conserve the biodiversity of rangelands ecosystems; and increase their resilience. Future analysis should consider the effects of rising temperatures and drought on rangeland degradation and productivity.
  • Sree, Sreesha; Parkkinen, Ilmari; Their, Anna; Airavaara, Mikko; Jokitalo, Eija (Multidisciplinary Digital Publishing Institute, 2021)
    The endoplasmic reticulum (ER) is a multipurpose organelle comprising dynamic structural subdomains, such as ER sheets and tubules, serving to maintain protein, calcium, and lipid homeostasis. In neurons, the single ER is compartmentalized with a careful segregation of the structural subdomains in somatic and neurite (axodendritic) regions. The distribution and arrangement of these ER subdomains varies between different neuronal types. Mutations in ER membrane shaping proteins and morphological changes in the ER are associated with various neurodegenerative diseases implying significance of ER morphology in maintaining neuronal integrity. Specific neurons, such as the highly arborized dopaminergic neurons, are prone to stress and neurodegeneration. Differences in morphology and functionality of ER between the neurons may account for their varied sensitivity to stress and neurodegenerative changes. In this review, we explore the neuronal ER and discuss its distinct morphological attributes and specific functions. We hypothesize that morphological heterogeneity of the ER in neurons is an important factor that accounts for their selective susceptibility to neurodegeneration.
  • Asghar, Muhammad Yasir; Lassila, Taru; Törnquist, Kid (Multidisciplinary Digital Publishing Institute, 2021)
    Calcium signaling participates in a vast number of cellular processes, ranging from the regulation of muscle contraction, cell proliferation, and mitochondrial function, to the regulation of the membrane potential in cells. The actions of calcium signaling are, thus, of great physiological significance for the normal functioning of our cells. However, many of the processes that are regulated by calcium, including cell movement and proliferation, are important in the progression of cancer. In the normal thyroid, calcium signaling plays an important role, and evidence is also being gathered showing that calcium signaling participates in the progression of thyroid cancer. This review will summarize what we know in regard to calcium signaling in the normal thyroid as, well as in thyroid cancer.
  • Seitsonen, Oula; Ikäheimo, Janne (Multidisciplinary Digital Publishing Institute, 2021)
    Open access airborne laser scanning (ALS) data have been available in Finland for over a decade and have been actively applied by the Finnish archaeologists in that time. The low resolution of this laser scanning 2008–2019 dataset (0.5 points/m<sup>2</sup>), however, has hindered its usability for archaeological prospection. In the summer of 2020, the situation changed markedly, when the Finnish National Land Survey started a new countrywide ALS survey with a higher resolution of 5 points/m<sup>2</sup>. In this paper we present the first results of applying this newly available ALS material for archaeological studies. Finnish LIDARK consortium has initiated the development of semi-automated approaches for visualizing, detecting, and analyzing archaeological features with this new dataset. Our first case studies are situated in the Alpine tundra environment of Sápmi in northern Finland, and the assessed archaeological features range from prehistoric sites to indigenous Sámi reindeer herding features and Second Word War-era German military structures. Already the initial analyses of the new ALS-5p data show their huge potential for locating, mapping, and assessing archaeological material. These results also suggest an imminent burst in the number of known archaeological sites, especially in the poorly accessible and little studied northern wilderness areas, when more data become available.
  • Aronniemi, Johanna; Långström, Satu; Mattila, Katariina A.; Mäkipernaa, Anne; Salminen, Päivi; Pitkäranta, Anne; Pekkola, Johanna; Lassila, Riitta (Multidisciplinary Digital Publishing Institute, 2021)
    Introduction: Venous malformations (VMs) are congenital low-flow lesions with a wide spectrum of clinical manifestations. An increasing number of studies link VMs to coagulation abnormalities, especially to elevated D-dimer and decreased fibrinogen. This condition, termed localized intravascular coagulopathy (LIC), may pose a risk for hemostatic complications. However, detailed data on the laboratory variables for coagulation and fibrinolytic activity in VM patients are limited. We addressed this question by systematically analyzing the coagulation parameters in pediatric VM patients. Methods: We included 62 patients (median age 11.9 years) with detailed laboratory tests for coagulation and fibrinolytic activity at a clinically steady phase. We assessed clinical and imaging features of VMs and their correlations with coagulation and fibrinolysis variables using patient records and MRI. Results: D-dimer was elevated in 39% and FXIII decreased in 20% of the patients, as a sign of LIC. Elevated D-dimer and decreased FXIII were associated with large size, deep location, and diffuse and multifocal VMs. FVIII was elevated in 17% of the patients and was associated with small VM size, superficial and confined location, discrete morphology, and less pain. Surprisingly, antithrombin was elevated in 55% of the patients but without associations with clinical or other laboratory variables. Conclusions: LIC was common in pediatric patients with VMs. Our results provide a basis for when evaluating the risks of hemostatic complications in children with VMs. Further research is warranted to explore the mechanisms behind coagulation disturbances and their relation to clinical complications.
  • Öörni, Katariina; Kovanen, Petri T. (Multidisciplinary Digital Publishing Institute, 2021)
    Circulating low-density lipoprotein (LDL) particles enter the arterial intima where they bind to the extracellular matrix and become modified by lipases, proteases, and oxidizing enzymes and agents. The modified LDL particles aggregate and fuse into larger matrix-bound lipid droplets and, upon generation of unesterified cholesterol, cholesterol crystals are also formed. Uptake of the aggregated/fused particles and cholesterol crystals by macrophages and smooth muscle cells induces their inflammatory activation and conversion into foam cells. In this review, we summarize the causes and consequences of LDL aggregation and describe the development and applications of an assay capable of determining the susceptibility of isolated LDL particles to aggregate when exposed to human recombinant sphingomyelinase enzyme ex vivo. Significant person-to-person differences in the aggregation susceptibility of LDL particles were observed, and such individual differences largely depended on particle lipid composition. The presence of aggregation-prone LDL in the circulation predicted future cardiovascular events in patients with atherosclerotic cardiovascular disease. We also discuss means capable of reducing LDL particles’ aggregation susceptibility that could potentially inhibit LDL aggregation in the arterial wall. Whether reductions in LDL aggregation susceptibility are associated with attenuated atherogenesis and a reduced risk of atherosclerotic cardiovascular diseases remains to be studied.
  • Hussein, Tareq; Alameer, Ali; Jaghbeir, Omar; Albeitshaweesh, Kolthoum; Malkawi, Mazen; Boor, Brandon E.; Koivisto, Antti Joonas; Löndahl, Jakob; Alrifai, Osama; Al-Hunaiti, Afnan (Multidisciplinary Digital Publishing Institute, 2021)
    The authors would like to correct the published article [...]
  • Pääkkönen, Markus; Pelkonen, Tuula; Joaquim, Guilhermino; Bernandino, Luis; Pöyhiä, Tiina; Roine, Irmeli; Peltola, Heikki (Multidisciplinary Digital Publishing Institute, 2021)
    We reviewed the characteristics of children hospitalized for bone and joint infections in Luanda, Angola. In a retrospective chart review of 45 patients with childhood osteomyelitis or septic arthritis, 51% of the patients had sickle cell disease, and these patients presented with lower hemoglobin and needed blood transfusion more frequently (<i>p</i> &lt; 0.05). Out of all patients, 64% underwent surgical procedures; a pathological fracture occurred in 31% of the patients.
  • Ahmed, Hammad; Khan, Mahtab Ahmad; Kahlert, Ulf Dietrich; Niemelä, Mika; Hänggi, Daniel; Chaudhry, Shafqat Rasul; Muhammad, Sajjad (Multidisciplinary Digital Publishing Institute, 2021)
    Myeloid differentiation 88 (MyD88) is a well-established inflammatory adaptor protein. It is one of the essential downstream proteins of the toll-like receptor 4 (TLR4) signaling pathway. TLRs are pattern recognition receptors that are usually activated by the damage-associated molecular pattern molecules (DAMPs). Sterile inflammation is triggered by the endogenous DAMPs released in response to global cerebral ischemia and from extravasated blood after subarachnoid hemorrhage (SAH). In this review, we highlight the importance of the neuroinflammatory role of the MyD88 in the SAH. We also explore a few possible pharmacological agents that can be used to decrease SAH-associated neuroinflammation by modulating the MyD88 dependent functions. Pharmacological agents such as flavonoids, melatonin, fluoxetine, pentoxifylline and progesterone have been investigated experimentally to reduce the SAH-associated inflammation. Inhibition of the MyD88 not only reduces the expression of pro-inflammatory cytokines, but also potentially inhibits other processes that can augment the SAH associated inflammation. Further investigations are required to translate these findings in the clinical setting.
  • Kellokumpu, Ilmo; Kairaluoma, Matti; Mecklin, Jukka-Pekka; Kellokumpu, Henrik; Väyrynen, Ville; Wirta, Erkki-Ville; Sihvo, Eero; Kuopio, Teijo; Seppälä, Toni T. (Multidisciplinary Digital Publishing Institute, 2021)
    This retrospective population-based study examined the impact of age and comorbidity burden on multimodal management and survival from colorectal cancer (CRC). From 2000 to 2015, 1479 consecutive patients, who underwent surgical resection for CRC, were reviewed for age-adjusted Charlson comorbidity index (ACCI) including 19 well-defined weighted comorbidities. The impact of ACCI on multimodal management and survival was compared between low (score 0–2), intermediate (score 3) and high ACCI (score ≥ 4) groups. Changes in treatment from 2000 to 2015 were seen next to a major increase of laparoscopic surgery, increased use of adjuvant chemotherapy and an intensified treatment of metastatic disease. Patients with a high ACCI score were, by definition, older and had higher comorbidity. Major elective and emergency resections for colon carcinoma were evenly performed between the ACCI groups, as were laparoscopic and open resections. (Chemo)radiotherapy for rectal carcinoma was less frequently used, and a higher rate of local excisions, and consequently lower rate of major elective resections, was performed in the high ACCI group. Adjuvant chemotherapy and metastasectomy were less frequently used in the ACCI high group. Overall and cancer-specific survival from stage I-III CRC remained stable over time, but survival from stage IV improved. However, the 5-year overall survival from stage I–IV colon and rectal carcinoma was worse in the high ACCI group compared to the low ACCI group. Five-year cancer-specific and disease-free survival rates did not differ significantly by the ACCI. Cox proportional hazard analysis showed that high ACCI was an independent predictor of poor overall survival (<i>p</i> &lt; 0.001). Our results show that despite improvements in multimodal management over time, old age and high comorbidity burden affect the use of adjuvant chemotherapy, preoperative (chemo)radiotherapy and management of metastatic disease, and worsen overall survival from CRC.
  • Järvelä, Aleksi; Tähtinen, Tero (Multidisciplinary Digital Publishing Institute, 2021)
    In this paper, we explore the historical background and the semantic underpinnings of a central, if marginally treated, metaphor of enlightenment and transmission in Chan discourse, “silent accord” 默契. It features centrally in <i>Essentials of the Transmission of Mind</i> 傳心法要, a text that gathers the teachings of Chan master Huangbo Xiyun (d. ca. 850), a major Tang dynasty figure. “Silent accord” is related to the concept of mind-to-mind transmission, which lies at the very core of Chan Buddhist self-understanding. However, Chan historiography has shown that this self-understanding was partially a product of the Song dynasty lineage records, historically retroactive syncretic constructs produced by monks and literati as efforts towards doctrinal and political recognition and orthodoxy. There are thus lacunae in the history of Chan thought opened up by the retrospective fictions of Song dynasty, and a lack of reliable, dateable documents from the preceding Tang dynasty era, possibly fraught with later additions. We situate the metaphor “silent accord” in the history of Chan thought by searching for its origins, mapping its functions in Chan literature, arguing for its influence and thereby its role in helping to bridge the ninth century gap.
  • Miah, Mohammad Yusuf; Hossain, Mohammad Mosarof; Schneider, Petra; Mozumder, Mohammad Mojibul Hoque; Mitu, Sabrina Jannat; Shamsuzzaman, Md. Mostafa (Multidisciplinary Digital Publishing Institute, 2021)
    The Meghna river estuary has had substantial importance in supporting the coastal community’s livelihood for decades, but the pressure on it is immense due to many anthropogenic drivers. The present study aimed to assess its ecosystem services (ES) according to the framework of the standard international classification of ecosystem services (CICES). This study also identified the drivers, pressure, state, impact, and responses (DPSIR), and the factors responsible for ES changes in the Meghna river estuarine ecosystems. By merging both quantitative and qualitative data, a total of 19 sub-categories of ES were found, among which eight are provisioning, seven are regulatory, and four are cultural services, according to the CICES framework. From the results, it can be concluded that food provisioning from the Hilsha fishery, the national fish as a part of cultural heritage, and nursery habitat functions were the top provisional, regulatory, and cultural services to the society in the study areas and beyond. However, several threats and stressors of both anthropogenic and natural origins were identified as drivers of ES changes, such as overexploitation, destructive and illegal fishing, heavy river bed siltation, and natural hazards such as extreme cyclonic events, floods, and sea levels rising. This study underlines the urgency of research and policy attention to address the challenges, and of transforming management regimes to an ecosystem-based approach, which is part of nature-based solutions according to the International Union for Conservation of Nature (IUCN), which refers to the present case, and particularly to fishery co-management. Creating alternative income sources and raising community awareness regarding the importance of maintaining the healthy condition of the river basins, and comprehensive compliance with the rules and regulations are proposed in order to ensure these estuarine ecosystems’ sustainability.
  • Räisänen, Ismo T.; Lähteenmäki, Hanna; Gupta, Shipra; Grigoriadis, Andreas; Sahni, Vaibhav; Suojanen, Juho; Seppänen, Hanna; Tervahartiala, Taina; Sakellari, Dimitra; Sorsa, Timo (Multidisciplinary Digital Publishing Institute, 2021)
    The aim of this cross-sectional study is to propose an efficient strategy based on biomarkers adjunct with an interview/questionnaire covering risk factors for periodontitis for the identification of undiagnosed periodontitis by medical professionals. Active matrix metalloproteinase (aMMP)-8 levels in mouthrinse were analyzed by a point-of-care (PoC)/chairside lateral-flow immunotest, and salivary total MMP-8, total MMP-9 and calprotectin levels were analyzed by enzyme-linked immunosorbent assays (ELISAs) and active MMP-9 by gelatin zymography for 149 Greek patients. Patients underwent a full-mouth oral health examination for diagnosis according to the 2018 classification system of periodontal diseases. In addition, patient characteristics (risk factors: age, gender, education level, smoking and body mass index) were recorded. Receiver operating curve (ROC) analysis indicated better diagnostic precision to identify undiagnosed periodontitis for oral fluid biomarkers in adjunct with an interview/questionnaire compared with a plain questionnaire (i.e., risk factors): aMMP-8 AUC (95% confidence interval) = 0.834 (0.761−0.906), total MMP-8 = 0.800 (0.722–0.878), active MMP-9 = 0.787 (0.704–0.870), total MMP-9 = 0.773 (0.687−0.858) and calprotectin = 0.773 (0.687–0.858) vs. questionnaire = 0.764 (0.676–0.851). The findings of this study suggest that oral fluid biomarker analysis, such as a rapid aMMP-8 PoC immunotest, could be used as an adjunct to an interview/questionnaire to improve the precision of timely identification of asymptomatic, undiagnosed periodontitis patients by medical professionals. This strategy appears to be viable for referring patients to a dentist for diagnosis and treatment need assessment.
  • Raza, Ahsan; Ahrends, Hella; Habib-Ur-Rahman, Muhammad; Gaiser, Thomas (Multidisciplinary Digital Publishing Institute, 2021)
    Information on soil erosion and related sedimentation processes are very important for natural resource management and sustainable farming. Plenty of models are available for studying soil erosion but only a few are suitable for dynamic soil erosion assessments at the field-scale. To date, there are no field-scale dynamic models available considering complex agricultural systems for the simulation of soil erosion. We conducted a review of 51 different models evaluated based on their representation of the processes of soil erosion by water. Secondly, we consider their suitability for assessing soil erosion for more complex field designs, such as patch cropping, strip cropping and agroforestry (alley-cropping systems) and other land management practices. Several models allow daily soil erosion assessments at the sub-field scale, such as EPIC, PERFECT, GUEST, EPM, TCRP, SLEMSA, APSIM, RillGrow, WaNuLCAS, SCUAF, and CREAMS. However, further model development is needed with respect to the interaction of components, i.e., rainfall intensity, overland flow, crop cover, and their scaling limitations. A particular shortcoming of most of the existing field scale models is their one-dimensional nature. We further suggest that platforms with modular structure, such as SIMPLACE and APSIM, offer the possibility to integrate soil erosion as a separate module/component and link to GIS capabilities, and are more flexible to simulate fluxes of matter in the 2D/3D dimensions. Since models operating at daily scales often do not consider a horizontal transfer of matter, such modeling platforms can link erosion components with other environmental components to provide robust estimations of the three-dimensional fluxes and sedimentation processes occurring during soil erosion events.
  • Juvela, Seppo (Multidisciplinary Digital Publishing Institute, 2021)
    The purpose was to study the risk of rupture of unruptured intracranial aneurysms (UIAs) of patients with multiple intracranial aneurysms after subarachnoid hemorrhage (SAH), in a long-term follow-up study, from variables known at baseline. Future rupture risk was compared in relation to outcome after SAH. The series consists of 131 patients with 166 UIAs and 2854 person-years of follow-up between diagnosis of UIA and its rupture, death or the last follow-up contact. These were diagnosed before 1979, when UIAs were not treated in our country. Those patients with a moderate or severe disability after SAH, according to the Glasgow Outcome Scale, had lower rupture rates of UIA than those with a good recovery or minimal disability (4/37 or 11%, annual UIA rupture rate of 0.5% (95% confidence interval (CI) 0.1–1.3%) during 769 follow-up years vs. 27/94 or 29%, 1.3% (95% CI 0.9–1.9%) during 2085 years). Those with a moderate or severe disability differed from others by their older age. Those with a moderate or severe disability tended to have a decreased cumulative rate of aneurysm rupture (log rank test, <i>p</i> = 0.066) and lower relative risk of UIA rupture (hazard ratio 0.39, 95% CI 0.14–1.11, <i>p</i> = 0.077). Multivariable hazard ratios showed at least similar results, suggesting that confounding factors did not have a significant effect on the results. The results of this study without treatment selection of UIAs suggest that patients with a moderate or severe disability after SAH have a relatively low risk of rupture of UIAs. Their lower treatment indication may also be supported by their known higher treatment risks.
  • Al-Hunaiti, Afnan; Ghazzy, Asma; Sweidan, Nuha; Mohaidat, Qassem; Bsoul, Ibrahim; Mahmood, Sami; Hussein, Tareq (Multidisciplinary Digital Publishing Institute, 2021)
    Here, we report on a phyto-mediated bimetallic (NiFe<sub>2</sub>O<sub>4</sub>) preparation using a <i>Boswellia carterii</i> extract, which was characterized by XRD, FT-IR, TGA, electron microscopy, magnetic spectroscopy, and Mössbauer spectroscopy measurements. The prepared nano-catalysts were tested for oxidation of lignin monomer molecules—vanillyl alcohol and cinnamyl alcohol. In comparison with previously reported methods, the nano NiFe<sub>2</sub>O<sub>4</sub> catalysts showed high photocatalytic activity and selectivity, under visible light irradiation with a nitroxy radical initiator (2,2,6,6-tetramethylpiperidinyloxy or 2,2,6,6-tetramethylpiperidine 1-oxyl; TEMPO) at room temperature and aerobic conditions. The multifold advantages of the catalyst both in terms of reduced catalyst loading and ambient temperature conditions were manifested by higher conversion of the starting material.
  • Sievänen, Tero; Törmäkangas, Timo; Laakkonen, Eija K.; Mecklin, Jukka-Pekka; Pylvänäinen, Kirsi; Seppälä, Toni T.; Peltomäki, Päivi; Sipilä, Sarianna; Sillanpää, Elina (Multidisciplinary Digital Publishing Institute, 2021)
    Lynch syndrome (LS) increases cancer risk. There is considerable individual variation in LS cancer occurrence, which may be moderated by lifestyle factors, such as body weight and physical activity (PA). The potential associations of lifestyle and cancer risk in LS are understudied. We conducted a retrospective study with cancer register data to investigate associations between body weight, PA, and cancer risk among Finnish LS carriers. The participants (<i>n</i> = 465, 54% women) self-reported their adulthood body weight and PA at 10-year intervals. Overall cancer risk and colorectal cancer (CRC) risk was analyzed separately for men and women with respect to longitudinal and near-term changes in body weight and PA using extended Cox regression models. The longitudinal weight change was associated with an increased risk of all cancers (HR 1.02, 95% CI 1.00–1.04) and CRC (HR 1.03, 1.01–1.05) in men. The near-term weight change was associated with a lower CRC risk in women (HR 0.96, 0.92–0.99). Furthermore, 77.6% of the participants retained their PA category over time. Men in the high-activity group had a reduced longitudinal cancer risk of 63% (HR 0.37, 0.15–0.98) compared to men in the low-activity group. PA in adulthood was not associated with cancer risk among women. These results emphasize the role of weight maintenance and high-intensity PA throughout the lifespan in cancer prevention, particularly in men with LS.
  • Hintikka, Jukka; Lensu, Sanna; Mäkinen, Elina; Karvinen, Sira; Honkanen, Marjaana; Lindén, Jere; Garrels, Tim; Pekkala, Satu; Lahti, Leo (Multidisciplinary Digital Publishing Institute, 2021)
    We have shown that prebiotic xylo-oligosaccharides (XOS) increased beneficial gut microbiota (GM) and prevented high fat diet-induced hepatic steatosis, but the mechanisms associated with these effects are not clear. We studied whether XOS affects adipose tissue inflammation and insulin signaling, and whether the GM and fecal metabolome explain associated patterns. XOS was supplemented or not with high (HFD) or low (LFD) fat diet for 12 weeks in male Wistar rats (<i>n</i> = 10/group). Previously analyzed GM and fecal metabolites were biclustered to reduce data dimensionality and identify interpretable groups of co-occurring genera and metabolites. Based on our findings, biclustering provides a useful algorithmic method for capturing such joint signatures. On the HFD, XOS-supplemented rats showed lower number of adipose tissue crown-like structures, increased phosphorylation of AKT in liver and adipose tissue as well as lower expression of hepatic miRNAs. XOS-supplemented rats had more fecal glycine and less hypoxanthine, isovalerate, branched chain amino acids and aromatic amino acids. Several bacterial genera were associated with the metabolic signatures. In conclusion, the beneficial effects of XOS on hepatic steatosis involved decreased adipose tissue inflammation and likely improved insulin signaling, which were further associated with fecal metabolites and GM.

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