Advances in experimental medicine and biology最新文献

The circadian fluctuation of body temperature is one of the most prominent and stable outputs of the circadian clock and plays an important role in maintaining optimal day-night energy homeostasis. The body temperature of homothermic animals is not strictly constant, but it shows daily oscillation within a range of 1-3 °C, which is sufficient to synchronize the clocks of peripheral tissues throughout the body. The thermal entrainment mechanisms of the clock are partly mediated by the action of the heat shock transcription factor and cold-inducible RNA-binding protein-both have the ability to affect clock gene expression. Body temperature in the poikilotherms is not completely passive to the ambient temperature change; they can travel to the place of preferred temperature in a manner depending on the time of their endogenous clock. Based on this behavior-level thermoregulation, flies exhibit a clear body temperature cycle. Noticeably, flies and mice share the same molecular circuit for the controlled body temperature; in both species, the calcitonin receptors participate in the formation of body temperature rhythms during the active phase and exhibit rather specific expression in subsets of clock neurons in the brain. We summarize knowledge on mutual relationships between body temperature regulation and the circadian clock.

One of the functions of peroxisomes is the oxidation of fatty acids (FAs). The importance of this function in our lives is evidenced by the presence of peroxisomal disorders caused by the genetic deletion of proteins involved in these processes. Unlike mitochondrial oxidation, peroxisomal oxidation is not directly linked to ATP production. What is the role of FA oxidation in peroxisomes? Recent studies have revealed that peroxisomes supply the building blocks for lipid synthesis in the endoplasmic reticulum and facilitate intracellular carbon recycling for membrane quality control. Accumulation of very long-chain fatty acids (VLCFAs), which are peroxisomal substrates, is a diagnostic marker in many types of peroxisomal disorders. However, the relationship between VLCFA accumulation and various symptoms of these disorders remains unclear. Recently, we developed a method for solubilizing VLCFAs in aqueous media and found that VLCFA toxicity could be mitigated by oleic acid replenishment. In this chapter, we present the physiological role of peroxisomal FA oxidation and the knowledge obtained from VLCFA-accumulating peroxisome-deficient cells.

Hard-to-heal wounds are an important public health issue worldwide, with a significant impact on the quality of life of patients. It is estimated that approximately 1-2% of the global population suffers from difficult wounds, which can be caused by a variety of factors such as trauma, infections, chronic diseases like diabetes or obesity, or poor health conditions. Hard-to-heal wounds are often characterized by a slow and complicated healing process, which can lead to serious complications such as infections, pressure ulcers, scar tissue formation, and even amputations. These complications can have a significant impact on the mobility, autonomy, and quality of life of patients, leading to an increase in healthcare and social costs associated with wound care. The preparation of the wound bed is a key concept in the management of hard-to-heal wounds, with the aim of promoting an optimal environment for healing. The TIME (Tissue, Infection/Inflammation, Moisture, Edge) model is a systematic approach used to assess and manage wounds in a targeted and personalized way. The concept of TIMER, expanding the TIME model, further focuses on regenerative processes, paying particular attention to promoting tissue regeneration and wound healing in a more effective and comprehensive way. The new element introduced in the TIMER model is "Regeneration", which highlights the importance of activating and supporting tissue regeneration processes to promote complete and lasting wound healing. Regenerative therapies can include a wide range of approaches, including cellular therapies, growth factors, bioactive biomaterials, stem cell therapies, and growth factor therapies. These therapies aim to promote the formation of new healthy tissues, reduce inflammation, improve vascularization, and stimulate cellular proliferation to accelerate wound closure and prevent complications. Thanks to continuous progress in research and development of regenerative therapies, more and more patients suffering from difficult wounds can benefit from innovative and promising solutions to promote faster and more effective healing, improve quality of life, and reduce the risk of long-term complications.

Acute infectious diarrhea (AID) is one of the most common diseases in pediatric age with relevant burden both in high and in low-income countries. Thanks to their direct action on enterocyte functions and indirect actions on the mucosal and systemic immune system and on intestinal microbiome, probiotics are an ideal intervention to treat AID in childhood. However, their efficacy is strictly related to strains and indications, and practitioners should take this information into account in clinical practice. This chapter summarizes the main mechanisms of action of probiotics in AID, with a focus on proof of efficacy supporting their use in prevention and treatment of childhood AID. The use of selected strains in appropriate doses is strongly recommended by guidelines of AID, based on compelling proofs of efficacy and safety. At present, therapy with probiotics of AID is probably the strongest indication for probiotic use in medicine. Their role in prevention of AID is however questionable in healthy population, whereas it should be considered in at-risk population. Evidence for prevention of diarrhea in day-care centers and communities is lacking, but consistent evidence supports efficacy in prevention of hospital acquired diarrhea. Finally, this chapter presents novelties on this topic, in particular the role of rotavirus immunization on probiotics effectiveness and the effect of probiotics and postbiotics on Covid-associated diarrhea.Overall: AID is the most convincing area for probiotic use in children with gastrointestinal disorders, and effective strains should be used early on after onset of symptoms.

Gum chewing is used in orofacial therapy to improve oral functions, such as a patient's chewing ability, bite force, tongue pressure, and lip closure strength. However, its effects on masseter muscle oxygen dynamics and muscle activity may vary with the hardness and features of the gum base. Therefore, when considering gum chewing for therapeutic purposes, it is essential to select gum of an appropriate hardness. This study aimed to elucidate the impact of gum hardness differences on masseter muscle tissue oxygen dynamics and muscle activity. We conducted a 120-s gum chewing study using three types of gum with different hardness levels on 11 healthy adult males. Each patient's masseter muscle tissue oxygen dynamics, muscle activity, and heart rate were measured, and the extent of masseter fatigue was assessed using a visual analogue scale (VAS). Per our findings, as gum hardness increased, significant reductions in oxygen saturation (StO₂) and significant increases in deoxyhaemoglobin (Deoxy-Hb) concentrations were observed in masseter muscle tissue oxygen dynamics. Likewise, muscle activity, heart rate, and muscle fatigue (according to VAS) also increased significantly as gum hardness increased. The findings of this study reveal that increasing gum base hardness not only affects masseter muscle tissue oxygen dynamics but also increases muscle activity, masseter fatigue, and heart rate. When selecting gum for orofacial therapy involving gum chewing exercises, it is crucial to choose the appropriate gum.

We measured changes in blood flow and oxygenation in the brachioradialis muscle using near-infrared spectroscopy (NIRS) during reversal of rocuronium-induced muscle relaxation with administration of sugammadex in patients (n = 25) under general anaesthesia, to investigate whether reversal of muscle relaxant-induced muscle relaxation increases oxygen metabolism in skeletal muscle under general anaesthesia. NIRS measurements, including oxy-haemoglobin (Hb), deoxyHb, total Hb concentration, tissue oxygen index, and various cardiopulmonary parameters, were recorded at four timepoints: T0 (baseline), 3 min before sugammadex administration; T1, immediately before sugammadex administration; T2, at complete recovery of muscle contractility; and T3, 3 min after T2. All measured values at each timepoint were compared using multiple comparison tests. The median values (quartile deviation; QD) (μmol/L) of oxyHb and deoxyHb at T0, T1, T2, and T3 were 0, -0.01 (0.14), -1.15 (0.54), and -1.52 (0.54), and 0, 0.11 (0.06), 0.86 (0.5), and 1.36 (0.61), respectively. The levels of oxyHb were significantly lower and those of deoxyHb were significantly higher at T2 and T3 when compared to those at T1, respectively (P < 0.01). There were no significant changes in other measurements. These results suggest that reversal of rocuronium-induced muscle relaxation by sugammadex slightly increases oxygen metabolism in the brachioradialis muscle. This study might support the clinical finding that administration of neuromuscular blockers decreases whole body oxygen consumption in patients receiving mechanical ventilation under general anaesthesia.

Mild hyperthermia at 39-43 °C for 30-60 min is applied locoregionally to improve the oxygenation status of recurrent breast cancers, thus enhancing the efficacy of radio-, chemo-, and immunotherapy. In this context, estimated (or even conflicting) data are often used in computational modelling of tumour oxygenation and simulation of O₂ transport. In this chapter, we present information that may help to improve adjuvant thermotherapy delivered immediately prior to radiotherapy of recurrent breast cancers. Data are preferentially derived from clinical investigations; in some cases, measurements in experimental breast cancers are included.The biophysical properties presented for healthy, mostly postmenopausal, human breast (composite glandular-adipose-fibrous tissue) measured under normothermic (NT) conditions and in therapeutically heated breast cancers include tissue water content and tissue density. In general, averaged values of parameters reported for NT conditions are higher in breast cancers than in normal breast tissue, i.e., all ratios breast cancer/normal breast are >1. Mean values observed in breast cancers during mild hyperthermia (mHT) are consistently higher than those in NT tumours. Parameters determining convective transports in healthy breast tissue and breast cancer include blood flow rates, blood volume, exchanging water space, arterio-venous shunt flow, interstitial fluid flow rate, interstitial fluid pressure, microvascular permeability, interstitial hydraulic conductivity, and interstitial flow velocity. In general, averaged values of parameters measured under NT conditions are higher in breast cancers than in healthy breast. Except for interstitial fluid pressure, these values increase upon mHT treatment of cancers. Prime factors determining and describing the oxygenation status of the healthy breast, and in NT- versus mHT-treated breast cancers, include: oxygen (O₂) delivery rates, O₂- extractions, O₂- consumption rates, subepidermal microvascular HbO₂, tissue oxygen solubility, oxygen diffusion coefficients, mean O₂ partial pressures pO₂, hypoxic fractions HF <5 mmHg, oxygen enhancement ratio, and mitochondrial ROS production. With the exception of the mean pO₂, O₂ extraction rate and tissue O₂ saturation all parameters listed are distinctly higher in breast cancers under NT conditions compared to normal breast. Mild hyperthermia results in therapeutically relevant improvements of the oxygenation status of cancers and enhances mitochondrial ROS production, thus improving radiosensitivity. Note: The oxygenation status of the healthy (postmenopausal) breast is very similar to that of the normal human subcutis.

This chapter provides an overview of how international students in the United States used media and interpersonal channels to communicate with family, friends, and each other during the COVID-19 pandemic. The chapter starts by discussing the challenges of international students during the health pandemic. It then provides a review of the role of media during a crisis. Factors influencing media use during the COVID-19 crisis include culture, personality, and time spent in a foreign country. Finally, the chapter ends by providing suggestions for how universities can better equip their international offices to deal with international students during challenging times such as the COVID-19 pandemic.

Recent advances in neonatal intensive care have improved the survival rates of extremely low-birth-weight infants (ELBWIs). However, there has been no obvious improvement in the proportion of survivors without sequelae. Therefore, the development of appropriate management methods for ELBWIs in the neonatal intensive care unit is important to improve outcomes. In this study, we utilised time-domain near-infrared spectroscopy (TD-NIRS) for deep brain monitoring in premature infants in the clinical setting and measured the heads of three ELBWIs once weekly using a TD-NIRS system in transmittance mode. We found that optical signals transmitted through the head were detectable in all ELBWIs. We also confirmed that the total haemoglobin concentration and tissue oxygen saturation decreased in the first month after birth, while the reduced scattering coefficient was not correlated with postmenstrual age. We anticipate that this TD-NIRS technique will be useful for clinical assessment of deep brain tissues for appropriate management of cerebral circulation of ELBWIs in the neonatal intensive care unit.

The function of immune cells is delicately regulated under a variety of molecular networks. Transcriptional intermediary factor 1 (TIF1) family proteins, consisting of TRIM24, TRIM28 and TRIM33, share a highly conserved RING domain that is essential for the regulation of protein ubiquitination functioning as E3 ubiquitin ligases. TIF1 family proteins are diversely expressed in different types of immune cells, and participate in the regulation of various of cellular functions including chromosome modification, DNA repair, tumor progression, and immunity. In this review, we summarized current studies on TIF1 family proteins' functions in the modulation of immune cell development, anti-infection immunity, cancer immunology, inflammation, and autoimmune diseases.