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Abstract

In this study, the ability of microRNA-1906 (miR-1906) to attenuate bone loss in osteoporosis was evaluated by measuring the effects of a miR-1906 mimic and inhibitor on the cellular toxicity and cell viability of MC3T3‐E1 cells. Bone marrow-derived macrophage (BMM) cells were isolated from female mice, and tartrate-resistant acid phosphatase signalling was performed in miR-1906 mimic-treated, receptor-activated nuclear factor kappa-B (NF-κB) ligand (RANKL)-induced osteoclasts. In-vivo, osteoporosis was induced by ovariectomy (OVX). Rats were treated with 500 nmol/kg of the miR-1906 mimic via intrathecal administration for 10 consecutive days following surgery. The effect of the miR-1906 mimic on bone mineral density (BMD) in OVX rats was observed in the whole body, lumbar vertebrae and femur. Levels of biochemical parameters and cytokines in the serum of miR-1906 mimic-treated OVX rats were analysed. The mRNA expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), p-38 and NF-κB in tibias of osteoporotic rats (induced by ovariectomy) was observed using quantitative reverse-transcription polymerase chain reaction. Treatment with the miR-1906 mimic reduced cellular toxicity and enhanced the cell viability of MC3T3‐E1 cells. Furthermore, osteoclastogenesis in miR-1906 mimic-treated, RANKL-induced osteoclast cells was reduced, whereas the BMD in the miR-1906 mimic-treated group was higher than in the OVX group of rats. Treatment with the miR-1906 mimic also increased levels of biochemical parameters and cytokines in the serum of ovariectomised rats. Finally, mRNA expression levels of TLR4, MyD88, p-38 and NF-κB were lower in the tibias of miR-1906 mimic-treated rats than in those of OVX rats. In conclusion, the miR-1906 mimic reduces bone loss in rats with ovariectomy-induced osteoporosis by regulating the TLR4/MyD88/NF‐κB pathway.

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Physiology International
Authors: Gholamreza Rezamand, Touraj Mahmoudi, Seidamir Pasha Tabaeian, Hamid Farahani, Fatemeh Shahinmehr, Hossein Nobakht, Reza Dabiri, Asadollah Asadi, Fariborz Mansour-Ghanaei, and Mohammad Reza Zali

Abstract

Background

Nonalcoholic fatty liver disease (NAFLD) is an emerging global chronic liver disease worldwide. Considering the powerful association between NAFLD, insulin resistance (IR) and obesity, as well as the key role of ghrelin in these metabolic disorders, we hypothesized that some single nucleotide polymorphisms (SNPs) of the ghrelin (GHRL) and ghrelin receptor (GHSR) genes might be associated with NAFLD.

Methods

We conducted a case-control retrospective study of 150 cases with biopsy-proven NAFLD and 155 controls. The diagnosis of NAFLD was established before the start of the genotyping process. All the 305 subjects were genotyped for GHRL SNP rs26802 or -501T>G and GHSR SNP rs572169 or Arg159Arg using the PCR-RFLP method.

Results

The GHRL rs26802 “GG” genotype compared with the “TT” genotype and “TT+TG” genotype appears to be a marker of decreased NAFLD susceptibility even after adjustment for confounding factors (P = 0.006; OR = 0.14, 95% CI = 0.03–0.56 and P = 0.003; OR = 0.16, 95% CI = 0.05–0.53, respectively). However, we observed no significant difference in genotype or allele frequencies between the cases and controls for GHSR SNP rs572169.

Conclusions

These findings proposed, for the first time, that the GHRL rs26802 “GG” genotype has a protective effect against NAFLD. Nonetheless, this observation warrants further investigations in other populations.

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Abstract

Background

Older adults with mild cognitive impairment (OAwMCI) present subtle balance and gait deficits along with subjective memory decline. Although these presentations might not affect activities of daily living (ADLs), they attribute to a two-folded increase in falls. While changes occurring in volitional balance control during ADLs have been extensively examined among OAwMCI, reactive balance control, required to recover from external perturbations, has received little attention. Therefore, this study examined reactive balance control in OAwMCI compared to their healthy counterparts.

Methods

Fifteen older adults with mild cognitive impairment (OAwMCI), fifteen cognitively intact older adults (CIOA) (>55 years), and fifteen young adults (18–30 years) were exposed to stance perturbations at three different intensities. Behavioral outcomes postural COM state stability, step length, step initiation, and step execution were computed.

Results

Postural COM state stability was the lowest in OAwMCI compared to CIOA and young adults, and it deteriorated at higher perturbation intensities (P < 0.001). Step length was the lowest among OAwMCI and was significantly different from young adults (P < 0.001) but not from CIOA. Unlike OAwMCI, CIOA and young adults increased their step length at higher perturbation intensities (P < 0.001). OAwMCI showed longer recovery step initiation times and shorter execution times compared to CIOA and young adults at higher perturbation intensities (P < 0.001).

Conclusion

OAwMCI exhibit exacerbated reactive instability and are unable to modulate their responses as the threat to balance control altered. Thus, they are at a significantly higher risk of falls than their healthy counterparts.

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Abstract

The perturbation of adipokinetic hormones, such as irisin, chemerin, and asprosin has been reported to participate in pathological conditions (e.g., insulin resistance) and chronic inflammation. However, exercise training has been long established as an effective intervention for prevention and treatment of these chronic and metabolic diseases. This study was to examine the effects of aerobic continuous training (ACT) and aerobic interval training (AIT) on irisin and chemerin levels of liver tissue (LT) and visceral adipose tissue (VAT), circulating asprosin, and their relationships with cardiometabolic risk factors in rats with metabolic syndrome (MetS). Thirty-two male Wistar rats were randomly divided into four equal groups: normal control (N-Ctr), control (Ctr-MetS), ACT, and AIT. After familiarization, rats with exercise intervention performed either ACT or AIT five times a week over eight weeks. The level of irisin in both ACT and AIT groups was higher than the Ctr-MetS group in LT and VAT, with a greater improvement of LT level observed in AIT vs. ACT groups. Furthermore, the level of chemerin in LT and VAT was lower in both ACT and AIT groups than the Ctr-MetS group, whereas only AIT group exhibited a reduction of serum asprosin when compared to ACT and Ctr-MetS, along with the improvements of cardiometabolic markers, such as HOMA-IR and lipid profile. These findings may support the efficiency and effectiveness of AIT intervention in the modulation of these novel metabolic hormones and cardiometabolic risk factors for reduced risk of metabolic syndrome.

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Abstract

Objective

To evaluate in-vivo and in-vitro effects of ferulic acid (FA) on glucocorticoid-induced osteoarthritis (GIO) to establish its possible underlying mechanisms.

Methods

The effects of FA on cell proliferation, cell viability (MTT assay), ALP activity, and mineralization assay, and oxidative stress markers (ROS, SOD, GSH LDH and MDA levels) were investigated by MC3T3-E1 cell line. Wistar rats received standard saline (control group) or dexamethasone (GC, 2 mg−1 kg) or DEX+FA (50 and 100 mg−1 kg) orally for 8 weeks. Bone density, micro-architecture, bio-mechanics, bone turnover markers and histo-morphology were determined. The expression of OPG, RANKL, osteogenic markers, and other signalling proteins was assessed employing quantitative RT-PCR and Western blotting.

Results

The findings indicated the elevation of ALP mRNA expressions, osteogenic markers (Runx-2, OSX, Col-I, and OSN), and the β-Catenin, Lrp-5 and GSK-3β protein expressions. FA showed the potential to increase MC3T3-E1 cell differentiation, proliferation, and mineralization. FA increased oxidative stress markers (SOD, MDA, and GSH) while decreasing ROS levels and lactate dehydrogenase release in GIO rats. The OPG/RANKL mRNA expression ratio was increased by FA, followed by improved GSK-3β and ERK phosphorylation with enhanced mRNA expressions of Lrp-5 and β-catenin.

Conclusion

These findings showed that FA improved osteoblasts proliferation with oxidative stress suppression by controlling the Lrp-5/GSK-3β/ERK pathway in GIO, demonstrating the potential pathways involved in the mechanism of actions of FA in GIO therapy.

Restricted access

Abstract

Psychedelic-assisted psychotherapy is an emerging psychiatric treatment that is attracting significant scientific, medical, and public attention. Whilst preliminary results from empirical studies are promising, the medical use of these compounds is highly controversial. Surprisingly, and despite the current controversies caused by the re-medicalisation of psychedelics, bioethicists have remained mysteriously silent. This paper aims to stimulate further bioethical reflection regarding the re-medicalisation of psychedelics. The current paper aims to do this by applying a normative phenomenological lens of analysis. Namely, this paper applies Martin Heidegger's critique of modern technology, and Fredrik Svenaeus' extension of this critique, to the re-medicalisation of psychedelics. I argue that when this critique of modern technology is applied several normative issues become apparent. Specifically, it becomes apparent that the re-medicalisation of psychedelics risks turning the ecological sources, cultural contexts, and experiences induced by psychedelics into resources to be exploited for human goals; all of which risks endangering ecosystems, appropriating traditional knowledge, and reducing the therapeutic effects of psychedelic-assisted psychotherapy. Furthermore, I suggest that preserving non-reductionist, non-instrumentalising traditional ways of understanding psychedelic compounds is essential in mitigating these consequences. More discussion by bioethicists is necessary as these consequences represent important global challenges for the psychedelic renaissance that require immediate addressing.

Open access

Abstract

Bacteria can enhance their survival by attaching to inanimate surfaces or tissues, and presenting as multicellular communities encased in a protective extracellular matrix called biofilm. There has been pronounced interest in assessing the relationship between the antibiotic resistant phenotype and biofilm-production in clinically-relevant pathogens. The aim of the present paper was to provide additional experimental results on the topic, testing the biofilm-forming capacity of Escherichia coli isolates using in vitro methods in the context of their antibiotic resistance in the form of a laboratory case study, in addition to provide a comprehensive review of the subject. In our case study, a total of two hundred and fifty (n = 250) E. coli isolates, originating from either clean-catch urine samples (n = 125) or invasive samples (n = 125) were included. The colony morphology of isolates were recorded after 24h, while antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Biofilm-formation of the isolates was assessed with the crystal violet tube-adherence method. Altogether 57 isolates (22.8%) isolates were multidrug resistant (MDR), 89 isolates (35.6%) produced large colonies (>3 mm), mucoid variant colonies were produced in 131 cases (52.4%), and 108 (43.2%) were positive for biofilm formation. Biofilm-producers were less common among isolates resistant to third-generation cephalosporins and trimethoprim-sulfamethoxazole (P = 0.043 and P = 0.023, respectively). Biofilms facilitate a protective growth strategy in bacteria, ensuring safety against environmental stressors, components of the immune system and noxious chemical agents. Being an integral part of bacterial physiology, biofilm-formation is interdependent with the expression of other virulence factors (especially adhesins) and quorum sensing signal molecules. More research is required to allow for the full understanding of the interplay between the MDR phenotype and biofilm-production, which will facilitate the development of novel therapeutic strategies.

Open access

Abstract

Background and aims

Cited in over 100 articles, the interactional model of exercise addiction (Egorov & Szabo, 2013) forms the theoretical foundation of many studies on the risk of exercise addiction. Still, the inclusion of previously omitted determinants could make it more useful. Therefore, this review presents the expanded version of the original model.

Method

We added ‘self-concept’ as another determinant in the ‘personal factors’ domain and ‘attractive alternatives’ to the ‘situational factors’ domain. Further, we doubled the reasons for exercise in the ‘incentives for exercise domain.’ Last, we added a new domain, the ‘exercise-related stressors,’ to illustrate that exercise itself might be a source of stress.

Results

The expanded model is more inclusive and accounts for a greater combination of interactions playing roles in exercise addiction. Overlooking the eventuality that stress resulting from exercise might also fuel the dysfunction was a significant omission from the original model, rectified in the current update. Finally, the new expansions make the model more applicable to competitive situations too

Conclusion

The expanded interactional model of exercise addiction is more comprehensive than its original version. It also accounts for the exercise or sport-related stress as possible fuel in addictive exercise behavior.

Open access

Abstract

The recently published Imperial College study of a Phase II, double-blind, randomized, controlled trial comparing psilocybin-assisted therapy to a six-week titration of escitalopram for Major Depressive Disorder (MDD) should raise concerns for this illness category as a target of early psychedelic research given a goal of FDA approval. There are three reasons why MDD is the wrong target at this stage of research development. Firstly, the psychiatric category of MDD is heterogeneous, vaguely-defined, and overdiagnosed in a way that will problematize finding a reliable signal with psychedelic interventions (or any intervention), particularly within non-severe cases. Secondly, current rating scales for MDD (QIDS used in the Imperial College trial, but also HAM-D) are limited in approximating the kinds of things we ultimately care most about with depressive states, namely functional status, quality of life, and well-being: measures that seem more salient for psychedelic interventions and which are not adequately captured by these rating scales used in a majority of clinical trials. And thirdly, there are inherent conflicts between psychiatric conceptualizations of MDD (and its symptom amelioration) and the kinds of perspectives on one’s suffering often occasioned by psychedelic experiences themselves: while these kinds of psychedelic-catalyzed openings may lead to a form of acceptance or equanimity with regards to one’s life circumstances this could be in many ways orthogonal to reductions in HAM-D scores. We argue that for these reasons MDD is a non-ideal target at this stage of the science and propose alternative directions.

Open access

By common consent, one of the most characteristic categories of the Polish verb is aspect. There can be little doubt that the origin of the aspect category may lie in Proto-Slavic or much further back in the Proto-Indo- European language. It is a moot point whether the aspect was already a strong category in Proto-Slavic. Nonetheless, it is beyond dispute that the consequences of its emergence were far-reaching and took a relatively long time to clarify in the daughter languages. The various categories such as aspect, biaspectuality, and tense providing the main themes of the present paper were closely related and did interact, however, the essential effects of their interaction can only be identified by scrutiny.

In Old Church Slavonic, a certain degree of competition between the category of aspect and that of tense can already be observed, and this is also evident in Old Polish, in which tenses like the aorist and the imperfect were slowly falling into disuse. Their occurrence is quite rare even in the earliest Polish written records. In due course, the perfect tense gained ground and the pluperfect became almost completely obsolete. In Modern Polish, the latter only serves to archaize literary texts. In the further stages of development, the aspectual opposition also extended to the future tenses thereby affecting the entire Polish tense system. Also, in the aspect-tense system of the Modern Polish language, the tendency of the category of aspect to prevail over the category of tense together with the gradual decline in the number of biaspectual verbs, still common in the 16th century, seems to be quite clear.

Most of the originally biaspectual initial verbs were later perfectivized by means of prefixes. Thus, the simple verbal bases and their perfectivized derivatives could establish an aspectual partnership. In the case of verbs with foreign roots, the prefix z-/ s- played a pivotal role in perfectivation, while other prefixes such as za- and po- had a less important role. The process of perfectivation in Polish was so extensive that only few biaspectual verbs remained free of the opposition of aspect as reminders of the fact that the development of this category is still an ongoing process. This is also shown by the more recent biaspectual verbs with borrowed roots for which it can be anticipated that they will form their perfective counterparts soon.

The paper concludes that the amount of verbs with an aspectually uncertain status is likely to be a reliable indicator of the development of the aspect category for the earlier periods in the history of the Polish language. An important role in this may play the diachronic corpus-based investigation, which, though for a long time considered a stepchild of Slavic aspectual research, may still help to clarify a number of issues related to the category of aspect.

Open access