Search

The significant correlation between ancient medicinal practices and brain function marks a revolutionary frontier in the field of neuroscience. Acupuncture, a traditional oriental medicine, can affect brain regions, such as the hypothalamus, anterior cingulate, posterior cingulate, and hippocampus, and produces specific therapeutic effects, such as pain relief, suppression of hypertension, and alleviation of drug addiction. Among the brain regions, the hypothalamus, a small yet critical region in the brain, plays a pivotal role in maintaining homeostasis by regulating a wide array of physiological processes, including stress responses, energy balance, and pain modulation. Emerging evidence suggests that acupuncture may exert its therapeutic effects by modulating the activity of the hypothalamus and its associated neural circuits, particularly in relation to pain, stress, and metabolic regulation. Thus, we conducted a comprehensive review of past and current research on the role of the hypothalamus in mediating the therapeutic effects of acupuncture. [ABSTRACT FROM AUTHOR]

This study aimed to show what role biomedical engineering can play in sexual health. A new concept of sexological ontology, an essential tool for building evidence-based models of sexual health, is proposed. This ontology should be based on properly validated mathematical models of sexual reactions identified using reliable measurements of physiological signals. This paper presents a review of the recommended measurement methods. Moreover, a general human sexual reaction model based on dynamic systems built at different levels of time × space × detail is presented, and the actual used modeling approaches are reviewed, referring to the introduced model. Lastly, examples of devices and computer programs designed for sexual therapy are described, indicating the need for legal regulation of their manufacturing, similar to that for other medical devices. [ABSTRACT FROM AUTHOR]

In several studies we have recently demonstrated that orgasm induces prolactin secretion in healthy males and females. This suggests that prolactin may form a feedback regulator of the refractory period following orgasm. To examine this position we investigated the prolactin response of a healthy multi-orgasmic male subject. Blood was drawn continuously during masturbation-induced orgasm. The prolactin response of the case-subject was compared with that of nine healthy adult men with a normal refractory period. The case-subject showed no prolactin response to three orgasms. Data from this multi-orgasmic subject support the hypothesized role of plasma prolactin in contributing to sexual-satiation mechanisms. [ABSTRACT FROM AUTHOR]

The high prevalence of diabetes mellitus (DM) poses a significant public health challenge, with diabetic kidney disease (DKD) as one of its most serious consequences. It has become increasingly clear that type 2 DM (T2D) and the complications of DKD are not purely metabolic disorders. This review outlines emerging evidence related to the step-by-step contribution of macrophages to the development and progression of DKD in individuals who specifically develop T2D as a result of obesity. The macrophage is a prominent inflammatory cell that contributes to obesity, where adipocyte hypertrophy leads to macrophage recruitment and eventually to the expansion of adipose tissue. The recruited macrophages secrete proinflammatory cytokines, which cause systemic inflammation, glucose dysregulation, and insulin sensitivity, ultimately contributing to the development of T2D. Under such pathological changes, the kidney is susceptible to elevated glucose and thereby activates signaling pathways that ultimately drive monocyte recruitment. In particular, the early recruitment of proinflammatory macrophages in the diabetic kidney produces inflammatory cytokines/chemokines that contribute to inflammation and tissue damage associated with DKD pathology. Macrophage activation and recruitment are crucial inciting factors that also persist as DKD progresses. Thus, targeting macrophage activation and function could be a promising therapeutic approach, potentially offering significant benefits for managing DKD at all stages of progression. [ABSTRACT FROM AUTHOR]

Poly L-lactic acid (PLLA) fillers stimulate collagen synthesis by activating various immune cells and fibroblasts. Piezo1, an ion channel, responds to mechanical stimuli, including changes in extracellular matrix stiffness, by mediating Ca2+ influx. Given that elevated intracellular Ca2+ levels trigger signaling pathways associated with fibroblast proliferation, Piezo1 is a pivotal regulator of collagen synthesis and tissue fibrosis. The aim of the present study was to investigate the impact of PLLA on dermal collagen synthesis by activating Piezo1 in both an H2O2-induced cellular senescence model in vitro and aged animal skin in vivo. PLLA elevated intracellular Ca2+ levels in senescent fibroblasts, which was attenuated by the Piezo1 inhibitor GsMTx4. Furthermore, PLLA treatment increased the expression of phosphorylated ERK1/2 to total ERK1/2 (pERK1/2/ERK1/2) and phosphorylated AKT to total AKT (pAKT/AKT), indicating enhanced pathway activation. This was accompanied by upregulation of cell cycle-regulating proteins (CDK4 and cyclin D1), promoting the proliferation of senescent fibroblasts. Additionally, PLLA promoted the expression of phosphorylated mTOR/S6K1/4EBP1, TGF-β, and Collagen I/III in senescent fibroblasts, with GsMTx4 treatment mitigating these effects. In aged skin, PLLA treatment similarly upregulated the expression of pERK1/2/ERK1/2, pAKT/AKT, CDK4, cyclin D1, mTOR/S6K1/4EBP1, TGF-β, and Collagen I/III. In summary, our findings suggest Piezo1′s involvement in PLLA-induced collagen synthesis, mediated by heightened activation of cell proliferation signaling pathways such as pERK1/2/ERK1/2, pAKT/AKT, and phosphorylated mTOR/S6K1/4EBP1, underscoring the therapeutic potential of PLLA in tissue regeneration. [ABSTRACT FROM AUTHOR]

Background: The molecular pathways involved in the onset and progression of idiopathic pulmonary fibrosis (IPF) still need to be fully clarified as some are shared with lung cancer development. HOXB7, a member of the homeobox (Hox) gene family, has been found involved in various cancers. Methods: Immunohistochemical (IHC) analysis was run on lung tissue samples from surgical lung biopsy (SLB) of 19 patients with IPF, retrospectively selected from the IPF database of the University Hospital of Modena. HOXB7 expression was analyzed and compared with that of five patients with no evidence of pulmonary fibrosis as controls. Results: The semi-quantitative analysis of IHC showed that HOXB7 protein expression was higher in IPF patients compared to controls (difference between means = 6.2 ± 2.37, p = 0.0157). Further, HOXB7 expression was higher in IPF patients with a higher extent of fibrosis (50–75%)—measured with high-resolution computer tomography—compared to those with a lower extent (0–25%) (difference between means = 25.74 ± 6.72, p = 0.004). Conclusions: The expression of HOXB7 is higher in the lung of IPF patients compared to controls, and was represented in different cellular compartments within the lung niche. Further investigations are needed to clarify its role in the pathogenesis and progression of IPF. [ABSTRACT FROM AUTHOR]

Orostachys japonicus is a popular traditional medicinal herb used in Asian countries. This study is focused on evaluating its role in lipid and glucose metabolism in cell and animal models to establish the plant as an anti-obesity and antidiabetic herb. A butanol fraction of O. japonicus was used in the study. The lipid production was evaluated by the Oil Red O technique while the expression of adipogenic markers by Western blotting and RT-PCR using 3T3-L1 preadipocyte. The effect on glucose uptake activity was evaluated in C2C12 myoblast cells. The animal study was carried out in C57BL mice to evaluate anti-obesity activity using the high-fat diet model. The evaluation of serum lipid, blood glucose, adipogenic and fibrosis markers in the liver, and fat deposition in the liver and adipose tissue (by histology) of mice was conducted. Butanol fraction of O. japonicus significantly inhibited the lipid production in the 3T3-L1 cells and reduced the expression of PPARγ, C/EBPα, SREBP-1c and aP2. It enhanced glucose uptake in insulin-resistant C2C12 myoblast cells. It reduced body weight, triglycerides, and blood glucose in the obese mice. It significantly inhibited lipid accumulation in the liver and adipose tissue of obese mice along with suppression of expression of adipogenic and fibrosis markers in the liver. In summary, supporting the previous results, this study helped to establish the potent anti-obesity, antidiabetic, and liver-protecting effect of the butanol fraction of O. japonicus. [ABSTRACT FROM AUTHOR]

The concept of targeted drug delivery can be described in terms of the drug systems' ability to mimic the biological objects' property to localize to target cells or tissues. For example, drug delivery systems based on red blood cells or mimicking some of their useful features, such as long circulation in stealth mode, have been known for decades. On the contrary, therapeutic strategies based on macrophages have gained very limited attention until recently. Here, we review two biomimetic strategies associated with macrophages that can be used to develop new therapeutic modalities: first, the mimicry of certain types of macrophages (i.e., the use of macrophages, including tumor-associated or macrophage-derived particles as a carrier for the targeted delivery of therapeutic agents); second, the mimicry of ligands, naturally absorbed by macrophages (i.e., the use of therapeutic agents specifically targeted at macrophages). We discuss the potential applications of biomimetic systems involving macrophages for new advancements in the treatment of infections, inflammatory diseases, and cancer. [ABSTRACT FROM AUTHOR]

Human activities have increased the intensity and frequency of natural stressors and created novel stressors, altering host–pathogen interactions and changing the risk of emerging infectious diseases. Despite the ubiquity of such anthropogenic impacts, predicting the directionality of outcomes has proven challenging. Here, we conduct a review and meta‐analysis to determine the primary mechanisms through which stressors affect host–pathogen interactions and to evaluate the impacts stress has on host fitness (survival and fecundity) and pathogen infectivity (prevalence and intensity). We assessed 891 effect sizes from 71 host species (representing seven taxonomic groups) and 78 parasite taxa from 98 studies. We found that infected and uninfected hosts had similar sensitivity to stressors and that responses varied according to stressor type. Specifically, limited resources compromised host fecundity and decreased pathogen intensity, while abiotic environmental stressors (e.g., temperature and salinity) decreased host survivorship and increased pathogen intensity, and pollution increased mortality but decreased pathogen prevalence. We then used our meta‐analysis results to develop susceptible–infected theoretical models to illustrate scenarios where infection rates are expected to increase or decrease in response to resource limitations or environmental stress gradients. Our results carry implications for conservation and disease emergence and reveal areas for future work. [ABSTRACT FROM AUTHOR]

Parasitic helminths induce a transient, short-term inflammation at the beginning of infection, but in persistent infection may suppress the systemic immune response by enhancing the activity of regulatory M2 macrophages. The aim of the study was to determine how nematode infection affects age-related neuroinflammation, especially macrophages in the nervous tissue. Here, intraperitoneal LPS-induced systemic inflammation resulting in brain neurodegeneration was enhanced by prolonged Heligmosomoides polygyrus infection in C57BL/6 mice. The changes in the brain coincided with the increase in M1 macrophages, reduced survivin level, enhanced APP and GFAP expression, chitin-like chains deposition in the brain and deterioration behaviour manifestations. These changes were also observed in transgenic C57BL/6 mice predisposed to develop neurodegeneration typical for Alzheimer's disease in response to pathogenic stimuli. Interestingly, in mice infected with the nematode only, the greater M2 macrophage population resulted in better results in the forced swim test. Given the growing burden of neurodegenerative diseases, understanding such interactive associations can have significant implications for ageing health strategies and disease monitoring. [ABSTRACT FROM AUTHOR]

Apoptosis and subsequent removal of dead cells are an essential part of wound healing. Macrophages phagocytize apoptotic cells (efferocytosis) and contribute to the resolution of inflammation. However, their participation in fibrogenesis and the mechanisms of influence on this process remain unclear. In the present study, we focused on the fibrogenic properties of human monocyte-derived macrophages polarized in the M2 direction by interaction with apoptotic cells. We studied their influence on the proliferation ([3H]-thymidine incorporation), differentiation (by the expression of α-SMA, a myofibroblast marker) and collagen-producing activity (ELISA) of dermal fibroblasts compared to classically (LPS) and alternatively (IL-4) activated macrophages. Macrophages polarized by the interaction with apoptotic cells had a unique phenotype and profile of produced factors and differed from the compared macrophage subtypes. Their conditioned media promoted the proliferation of dermal fibroblasts and the expression of α-SMA in them at the level of macrophages stimulated by IL-4, while the stimulating effect on the collagen-producing activity was more pronounced compared to that of the other macrophage subtypes. Moreover, they are characterized by the high level of production of pro-fibrotic factors such as TIMP-1, TGF-β1 and angiogenin. Taken together, M2-like macrophages polarized by efferocytosis demonstrate in vitro pro-fibrotic activity by promoting the functional activity of dermal fibroblasts and producing pro-fibrotic and pro-angiogenic factors. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common multidimensional neurological disorder characterized by motor and non-motor features and is more prevalent in the elderly. Sleep disorders and cognitive disturbances are also significant characteristics of PD. Sleep is an important physiological process for normal human cognition and physical functioning. Sleep deprivation negatively impacts human physical, mental, and behavioral functions. Sleep disturbances include problems falling asleep, disturbances occurring during sleep, abnormal movements during sleep, insufficient sleep, and excessive sleep. The most recognizable and known sleep disorders, such as rapid-eye-movement behavior disorder (RBD), insomnia, excessive daytime sleepiness (EDS), restless legs syndrome (RLS), sleep-related breathing disorders (SRBDs), and circadian-rhythm-related sleep–wake disorders (CRSWDs), have been associated with PD. RBD and associated emotional disorders are common non-motor symptoms of PD. In individuals, sleep disorders and cognitive impairment are important prognostic factors for predicting progressing neurodegeneration and developing dementia conditions in PD. Studies have focused on RBD and its associated neurological changes and functional deficits in PD patients. Other risks, such as cognitive decline, anxiety, and depression, are related to RBD. Sleep-disorder diagnosis is challenging, especially in identifying the essential factors that disturb the sleep–wake cycle and the co-existence of other concomitant sleep issues, motor symptoms, and breathing disorders. Focusing on sleep patterns and their disturbances, including genetic and other neurochemical changes, helps us to better understand the central causes of sleep alterations and cognitive functions in PD patients. Relations between α-synuclein aggregation in the brain and gender differences in sleep disorders have been reported. The existing correlation between sleep disorders and levels of α-synuclein in the cerebrospinal fluid indicates the risk of progression of synucleinopathies. Multidirectional approaches are required to correlate sleep disorders and neuropsychiatric symptoms and diagnose sensitive biomarkers for neurodegeneration. The evaluation of sleep pattern disturbances and cognitive impairment may aid in the development of novel and effective treatments for PD. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) refers to chronic progressive fibrotic interstitial pneumonia. It is called a "tumor-like disease" and cannot be cured using existing clinical drugs. Therefore, new treatment options are urgently needed. Studies have proven that ferroptosis is closely related to the development of IPF, and ferroptosis inhibitors can slow down the occurrence of IPF by chelating iron or reducing lipid peroxidation. For example, the ferroptosis inhibitor deferoxamine (DFO) was used to treat a mouse model of pulmonary fibrosis, and DFO successfully reversed the IPF phenotype and increased the survival rate of mice from 50% to 90%. Given this, we perceive that the treatment of IPF by delivering ferroptosis inhibitors is a promising option. However, the delivery of ferroptosis inhibitors faces two bottlenecks: low solubility and targeting. For one thing, we consider preparing ferroptosis inhibitors into nanomedicines to improve solubility. For another thing, we propose to deliver nanomedicines through pulmonary drug-delivery system (PDDS) to improve targeting. Compared with oral or injection administration, PDDS can achieve better delivery and accumulation in the lung, while reducing the systemic exposure of the drug, and is an efficient and safe drug-delivery method. In this paper, three possible nanomedicines for PDDS and the preparation methods thereof are proposed to deliver ferroptosis inhibitors for the treatment of IPF. Proper administration devices and challenges in future applications are also discussed. In general, this perspective proposes a promising strategy for the treatment of IPF based on inhalable nanomedicines carrying ferroptosis inhibitors, which can inspire new ideas in the field of drug development and therapy of IPF. [ABSTRACT FROM AUTHOR]

CCL2 is an inflammatory cytokine that regulates macrophage activity and is implicated in increased mammographic density and early breast tumorigenesis. The role of CCL2 in mediating stromal interactions that contribute to breast tumorigenesis has yet to be fully elucidated. THP-1-derived macrophages and mammary fibroblasts were co-cultured for 72 h. Fibroblasts and macrophages were analysed for phenotype, expression of inflammatory and ECM-regulatory genes and collagen production. Mice overexpressing CCL2 in the mammary glands were analysed for global gene expression by RNAseq at 12 weeks of age. These mice were cross-bred with PyMT mammary tumour mice to examine the role of CCL2 in tumorigenesis. The co-culture of macrophages with fibroblasts resulted in macrophage polarization towards an M2 phenotype, and upregulated expression of CCL2 and other genes associated with inflammation and ECM remodelling. CCL2 increased the production of insoluble collagen by fibroblasts. A global gene expression analysis of CCL2 overexpressing mice revealed that CCL2 upregulates cancer-associated gene pathways and downregulates fatty acid metabolism gene pathways. In the PyMT mammary tumour model, CCL2 overexpressing mice exhibited increased macrophage infiltration and early tumorigenesis. Interactions between macrophages and fibroblasts regulated by CCL2 can promote an environment that may increase breast cancer risk, leading to enhanced early tumorigenesis. [ABSTRACT FROM AUTHOR]

The understanding of macrophages and their pathophysiological role has dramatically changed within the last decades. Macrophages represent a very interesting cell type with regard to biomaterial-based tissue engineering and regeneration. In this context, macrophages play a crucial role in the biocompatibility and degradation of implanted biomaterials. Furthermore, a better understanding of the functionality of macrophages opens perspectives for potential guidance and modulation to turn inflammation into regeneration. Such knowledge may help to improve not only the biocompatibility of scaffold materials but also the integration, maturation, and preservation of scaffold-cell constructs or induce regeneration. Nowadays, macrophages are classified into two subpopulations, the classically activated macrophages (M1 macrophages) with pro-inflammatory properties and the alternatively activated macrophages (M2 macrophages) with anti-inflammatory properties. The present narrative review gives an overview of the different functions of macrophages and summarizes the recent state of knowledge regarding different types of macrophages and their functions, with special emphasis on tissue engineering and tissue regeneration. [ABSTRACT FROM AUTHOR]

During disease or toxin challenges, the behavioral activities of grazing animals alter in response to adverse situations, potentially providing an indicator of their welfare status. Behavioral changes such as feeding behavior, rumination and physical behavior as well as expressive behavior, can serve as indicators of animal health and welfare. Sometimes behavioral changes are subtle and occur gradually, often missed by infrequent visual monitoring until the condition becomes acute. There is growing popularity in the use of sensors for monitoring animal health. Acceleration sensors have been designed to attach to ears, jaws, noses, collars and legs to detect the behavioral changes of cattle and sheep. So far, some automated acceleration sensors with high accuracies have been found to have the capacity to remotely monitor the behavioral patterns of cattle and sheep. These acceleration sensors have the potential to identify behavioral patterns of farm animals for monitoring changes in behavior which can indicate a deterioration in health. Here, we review the current automated accelerometer systems and the evidence they can detect behavioral patterns of animals for the application of potential directions and future solutions for automatically monitoring and the early detection of health concerns in grazing animals. [ABSTRACT FROM AUTHOR]

Titanium is usually used in the manufacturing of metal implants due to its biocompatibility and high resistance to corrosion. A structural and functional connection between the living bone and the surface of the implant, a process called osseointegration, is mandatory for avoiding prolonged healing, infections, and tissue loss. Therefore, osseointegration is crucial for the success of the implantation procedure. Osseointegration is a process mediated by bone-matrix progenitor cells' proteins, named integrins. In this study, we used an in silico approach to assemble and test peptides that can be strategically used in sensitizing TiO2 implants in order to improve osseointegration. To do so, we downloaded PDB structures of integrins α5β1, αvβ3, and αIIbβ3; their biological ligands; and low-cost proteins from the Protein Data Bank, and then we performed a primary (integrin-protein) docking analysis. Furthermore, we modeled complex peptides with the potential to bind to the TiO2 surface on the implant, as well as integrins in the bone-matrix progenitor cells. Then we performed a secondary (integrin–peptide) docking analysis. The ten most promising integrin–peptide docking results were further verified by molecular dynamics (MD) simulations. We recognized 82 peptides with great potential to bind the integrins, and therefore to be used in coating TiO2 implants. Among them, peptides 1 (GHTHYHAVRTQTTGR), 3 (RKLPDATGR), and 8 (GHTHYHAVRTQTLKA) showed the highest binding stability during the MD simulations. This bioinformatics approach saves time and more effectively directs in vitro studies. [ABSTRACT FROM AUTHOR]

Prolactinomas are the commonest form of pituitary neuroendocrine tumor (PitNET), representing approximately half of such tumors. Dopamine agonists (DAs) have traditionally been the primary treatment for the majority of prolactinomas, with surgery considered the second line. The aim of this review is to examine the historical and modern management of prolactinomas, including medical therapy with DAs, transsphenoidal surgery, and multimodality therapy for the treatment of aggressive prolactinomas and metastatic PitNETs, with an emphasis on the efficacy, safety, and future directions of current therapeutic modalities. DAs have been the mainstay of prolactinoma management since the 1970s, initially with bromocriptine and more recently with cabergoline. Cabergoline normalizes prolactin in up to 85% of patients and causes tumor shrinkage in up to 80%. Primary surgical resection of microprolactinomas and enclosed macroprolactinomas performed by experienced pituitary neurosurgeons have similar remission rates to cabergoline. Aggressive prolactinomas and metastatic PitNETS should receive multimodality therapy including high dose cabergoline, surgery, radiation therapy (preferably using stereotactic radiosurgery where suitable), and temozolomide. DAs remain a reliable mode of therapy for most prolactinomas but results from transsphenoidal surgery in expert hands have improved considerably over the last one to two decades. Surgery should be strongly considered as primary therapy, particularly in the setting of microprolactinomas, non-invasive macroprolactinomas, or prior to attempting pregnancy, and has an important role in the management of DA resistant and aggressive prolactinomas. [ABSTRACT FROM AUTHOR]

Simple Summary: Sexual dysfunctions are rarely discussed in our current society. Males experience different sexual dysfunctions, including erectile, infertility, and ejaculatory dysfunctions. In this review only the ejaculatory dysfunction will be discussed. Ejaculation is defined as the ejection of contents collectively from the vas deferens, seminal vesicle, prostate and Cowper's glands. It is completely controlled by a population of neurons present in the lumbar spinal cord. The presence of lesion in these neurons ceases the ejaculatory behavior in males. This population of neurons was first identified in rats; however, recently it was confirmed that these neurons are present in human males as well. The issues are known as ejaculatory dysfunction. The following are the different types of ejaculatory dysfunctions: early ejaculation, ejaculation into the urinary bladder, late ejaculation and no ejaculation. Ejaculation is a reflex and the last stage of intercourse in male mammals. It consists of two coordinated phases, emission and expulsion. The emission phase consists of secretions from the vas deferens, seminal vesicle, prostate, and Cowper's gland. Once these contents reach the posterior urethra, movement of the contents becomes inevitable, followed by the expulsion phase. The urogenital organs are synchronized during this complete event. The L3–L4 (lumbar) segment, the spinal cord region responsible for ejaculation, nerve cell bodies, also called lumbar spinothalamic (LSt) cells, which are denoted as spinal ejaculation generators or lumbar spinothalamic cells [Lst]. Lst cells activation causes ejaculation. These Lst cells coordinate with [autonomic] parasympathetic and sympathetic assistance in ejaculation. The presence of a spinal ejaculatory generator has recently been confirmed in humans. Different types of ejaculatory dysfunction in humans include premature ejaculation (PE), retrograde ejaculation (RE), delayed ejaculation (DE), and anejaculation (AE). The most common form of ejaculatory dysfunction studied is premature ejaculation. The least common forms of ejaculation studied are delayed ejaculation and anejaculation. Despite the confirmation of Lst in humans, there is insufficient research on animals mimicking human ejaculatory dysfunction. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited therapeutic options. Macrophages, particularly alternatively activated macrophages (M2), have been recognized to contribute to the pathogenesis of pulmonary fibrosis. Therefore, targeting macrophages might be a viable therapeutic strategy for IPF. Herein, we report a potential nanomedicine-based gene therapy for IPF by modulating macrophage M2 activation. In this study, we illustrated that the levels of pleckstrin homology and FYVE domain containing 1 (Plekhf1) were increased in the lungs originating from IPF patients and PF mice. Further functionality studies identified the pivotal role of Plekhf1 in macrophage M2 activation. Mechanistically, Plekhf1 was upregulated by IL-4/IL-13 stimulation, after which Plekhf1 enhanced PI3K/Akt signaling to promote the macrophage M2 program and exacerbate pulmonary fibrosis. Therefore, intratracheal administration of Plekhf1 siRNA-loaded liposomes could effectively suppress the expression of Plekhf1 in the lungs and notably protect mice against BLM-induced lung injury and fibrosis, concomitant with a significant reduction in M2 macrophage accumulation in the lungs. In conclusion, Plekhf1 may play a crucial role in the pathogenesis of pulmonary fibrosis, and Plekhf1 siRNA-loaded liposomes might be a promising therapeutic approach against pulmonary fibrosis., (© 2023. Science China Press.)

Schistosomiasis is a chronic helminthic disease of both humans and animals and the second most prevalent parasitic disease after malaria. Through a complex migration process, schistosome eggs trapped in the liver can lead to the formation of granulomas and subsequent schistosome-induced liver damage, which results in high mortality and morbidity. Although praziquantel can eliminate mature worms and prevent egg deposition, effective drugs to reverse schistosome-induced liver damage are scarce. High mobility group box 1 (HMGB1) is a multifunctional cytokine contributing to liver injury, inflammation, and immune responses in schistosomiasis by binding to cell-surface Toll-like receptors and receptors for advanced glycation end products. HMGB1 is increased in the serum of patients with schistosomiasis and enables hepatic stellate cells to adopt a proliferative myofibroblast-like phenotype, which is crucial to schistosome-induced granuloma formation. Inhibition of HMGB1 was found to generate protective responses against fibrotic diseases in animal models. Clinically, HMGB1 presents a potential target for treatment of the chronic sequelae of schistosomiasis. Here, the pivotal role of HMGB1 in granuloma formation and schistosome-induced liver damage, as well the potential of HMGB1 as a therapeutic target, are discussed. [ABSTRACT FROM AUTHOR]

Along with its many advantages, social roosting imposes a major risk of pathogen transmission. How social animals reduce this risk is poorly documented. We used lipopolysaccharide challenge to imitate bacterial infection in both a captive and a free‐living colony of an extremely social, long‐lived mammal—the Egyptian fruit bat. We monitored behavioral and physiological responses using an arsenal of methods, including onboard GPS to track foraging, acceleration sensors to monitor movement, infrared video to record social behavior, and blood samples to measure immune markers. Sick‐like (immune‐challenged) bats exhibited an increased immune response, as well as classic illness symptoms, including fever, weight loss, anorexia, and lethargy. Notably, the bats also exhibited behaviors that would reduce pathogen transfer. They perched alone and appeared to voluntarily isolate themselves from the group by leaving the social cluster, which is extremely atypical for this species. The sick‐like individuals in the open colony ceased foraging outdoors for at least two nights, thus reducing transmission to neighboring colonies. Together, these sickness behaviors demonstrate a strong, integrative immune response that promotes recovery of infected individuals while reducing pathogen transmission inside and outside the roost, including spillover events to other species, such as humans. [ABSTRACT FROM AUTHOR]

Prolactin has been shown to favor both the activation and suppression of the microglia and astrocytes, as well as the release of inflammatory and anti-inflammatory cytokines. Prolactin has also been associated with neuronal damage in diseases such as multiple sclerosis, epilepsy, and in experimental models of these diseases. However, studies show that prolactin has neuroprotective effects in conditions of neuronal damage and inflammation and may be used as neuroprotector factor. In this review, we first discuss general information about prolactin, then we summarize recent findings of prolactin function in inflammatory and anti-inflammatory processes and factors involved in the possible dual role of prolactin are described. Finally, we review the function of prolactin specifically in the central nervous system and how it promotes a neuroprotective effect, or that of neuronal damage, particularly in experimental autoimmune encephalomyelitis and during excitotoxicity. The overall studies indicated that prolactin may be a promising molecule for the treatment of some neurological diseases. [ABSTRACT FROM AUTHOR]

Controlled wound healing requires a temporal and spatial coordination of cellular activities within the surrounding extracellular matrix (ECM). Disruption of cell-cell and cell-matrix communication results in defective repair, like chronic or fibrotic wounds. Activities of macrophages and fibroblasts crucially contribute to the fate of closing wounds. To investigate the influence of the ECM as an active part controlling cellular behavior, coculture models based on fibrillar 3D biopolymers such as collagen have already been successfully used. With well-defined biochemical and biophysical properties such 3D scaffolds enable in vitro studies on cellular processes including infiltration and differentiation in an in vivo like microenvironment. Further, paracrine and autocrine signaling as well as modulation of soluble mediator transport inside the ECM can be modeled using fibrillar 3D scaffolds. Herein, we review the usage of these scaffolds in in vitro coculture models allowing in-depth studies on the crosstalk between macrophages and fibroblasts during different stages of cutaneous wound healing. A more accurate mimicry of the various processes of cellular crosstalk at the different stages of wound healing will contribute to a better understanding of the impact of biochemical and biophysical environmental parameters and help to develop further strategies against diseases such as fibrosis., (© 2021 Franziska Ullm and Tilo Pompe, published by De Gruyter, Berlin/Boston.)

Few studies have investigated placebo and nocebo effects in a human sexuality context. Studying placebo and nocebo responses in this context may provide insight into their potential to modulate sexual drive and function. To examine such effects in sexual medicine, 48 healthy, male heterosexual participants were divided into four groups. Each group received instruction to expect stimulating effects, no effect, or an inhibitory effect on sexual functions. Only one group received the dopamine agonist cabergoline; all other groups received placebo or nocebo. Modulations in sexual experience were examined through an established experimental paradigm of sexual arousal and masturbation-induced orgasm during erotic film sequences with instruction to induce placebo or nocebo effects. Endocrine data, appetitive, consummatory, and refractory sexual behavior parameters were assessed using the Arizona Sexual Experience Scale (ASEX) and the Acute Sexual Experience Scale (ASES). Results showed increased levels of sexual function after administration of cabergoline with significant effects for several parameters. Placebo effects were induced only to a small degree. No negative effects on sexual parameters in the nocebo condition were noted. This paradigm could induce only small placebo and nocebo effects. This supports the view that healthy male sexual function seems relatively resistant to negative external influences. [ABSTRACT FROM AUTHOR]

Background and Objective: Communication between patients and health care practitioners is expected to benefit health outcomes. The objective of this review was to assess the effects of experimentally varied communication on clinical patients' pain.Databases and Data Treatment: We searched in July 2012, 11 databases supplemented with forward and backward searches for (quasi-) randomized controlled trials in which face-to-face communication was manipulated. We updated in June 2015 using the four most relevant databases (CINAHL, Cochrane Central, Psychinfo, PubMed).Results: Fifty-one studies covering 5079 patients were included. The interventions were separated into three categories: cognitive care, emotional care, procedural preparation. In all but five studies the outcome concerned acute pain. We found that, in general, communication has a small effect on (acute) pain. The 19 cognitive care studies showed that a positive suggestion may reduce pain, whereas a negative suggestion may increase pain, but effects are small. The 14 emotional care studies showed no evidence of a direct effect on pain, although four studies showed a tendency for emotional care lowering patients' pain. Some of the 23 procedural preparation interventions showed a weak to moderate effect on lowering pain.Conclusions: Different types of communication have a significant but small effect on (acute) pain. Positive suggestions and informational preparation seem to lower patients' pain. Communication interventions show a large variety in quality, complexity and methodological rigour; they often used multiple components and it remains unclear what the effective elements of communication are. Future research is warranted to identify the effective components. [ABSTRACT FROM AUTHOR]

During laboratory gambling tasks participants are not typically allowed to wager their personal wealth. Instead, wealth is simulated by telling participants they have been endowed with game tokens that will be later exchanged for money. Past research indicates that participants undervalue game tokens following this procedure, which leads to elevated risk taking compared to procedures that add saliency or realism to the monetary payoff. A between-subjects experiment tested whether showing a picture of money during the endowment instructions and repeating token-money exchange information during the session influenced participants' preference for risky and riskless options. The results showed no effect of the money picture. However, repeated token-money exchange information significantly decreased risk taking. Together with past studies, this finding suggests that endowment procedures might establish greater value in game tokens, and therefore better simulate personal wealth, when the eventual exchange between game tokens and money is made more salient to participants. [ABSTRACT FROM AUTHOR]

Polypropylene mesh is commonly used in the treatment of abdominal hernia. Different approaches were addressed to improve their tissue integration and consequently reduce long-term complications. This study aimed to investigate the effect of alpha-lipoic acid ( ALA) co-administration on structural and immunohistochemical ( IHC) changes in the subcutaneous tissues of the anterior abdominal wall of the adult rat in response to polypropylene mesh implantation. Forty adult male albino rats were divided into: group I (control), group II (receiving ALA), group III (polypropylene mesh implantation) and group IV (mesh implantation + ALA co-administration). After 4 weeks, subcutaneous tissue samples were prepared for light microscopy and IHC study of CD34 as a marker for angiogenesis. In groups I and II rats, positive CD34 expression was demonstrated by IHC reaction, localized to endothelial cells lining small blood vessels. Group III showed an excess inflammatory reaction, deposition of both regular and irregularly arranged collagen fibres around mesh pores and few elastic fibres. CD34-positive was detected not only in cells lining small blood vessels but also in other cells scattered in the connective tissue indicating angiogenesis. In group IV, ALA co-administration resulted in less inflammatory reaction, regular collagen deposition, enhanced elastic fibres synthesis and a significant increase in CD34-positive cells and small blood vessels reflecting improved angiogenesis. ALA co-administration with polypropylene mesh implantation controlled the inflammatory reaction, helped regular collagen deposition, enhanced elastic fibres synthesis and improved angiogenesis in the subcutaneous tissue of anterior abdominal wall of adult albino rats, suggesting a possible role of ALA in optimizing mesh integration in subcutaneous tissue. [ABSTRACT FROM AUTHOR]

Animals balance their intake of specific nutrients, but little is known about how they do so when foraging in an environment with toxic resources and whether toxic foods promote adaptations that affect life history traits. In German cockroach ( Blattella germanica) populations, glucose aversion has evolved in response to glucose-containing insecticidal baits. We restricted newly eclosed glucose-averse ( GA) and wild-type ( WT) female cockroaches to nutritionally defined diets varying in protein-to-carbohydrate (P : C) ratio (3 : 1, 1 : 1, or 1 : 3) or gave them free choice of the 3 : 1 and 1 : 3 diets, with either glucose or fructose as the sole carbohydrate source. We measured consumption of each diet over 6 days and then dissected the females to measure the length of basal oocytes in their ovaries. Our results showed significantly lower consumption by GA compared to WT cockroaches when restricted to glucose-containing diets, but also lower fructose intake by GA compared to WT cockroaches when restricted to high fructose diets or given choice of fructose-containing diets. Protein intake was regulated tightly regardless of carbohydrate intake, except by GA cockroaches restricted to glucose-containing diets. Oocyte growth was completely suppressed in GA females restricted to glucose-containing diets, but also significantly slower in GA than in WT females restricted to fructose-containing diets. Our findings suggest that GA cockroaches have adapted to reduced diet breadth through endocrine adjustments which reduce requirements for energetic fuels. Our study illustrates how an evolutionary change in the chemosensory system may affect the evolution of other traits that govern animal life histories. [ABSTRACT FROM AUTHOR]

Akin to other physiological responses, immune functions can be modified through behavioral conditioning as part of a learned placebo response. However, like every learning process, learned immune responses are subject to extinction. We analyzed the extinction of learned immunosuppression in healthy male volunteers, using an established conditioning paradigm with the immunosuppressive drug cyclosporin A (CsA) as unconditioned stimulus (US) and a gustatory stimulus as conditioned stimulus (CS). We observed a learned suppression of T-cell function after two and four reexposures to the CS, which was extinguished after 14 unreinforced CS reexposures. However, administration of 'subtherapeutic' CsA dosages together with the CS counteracted the extinction of the learned immunosuppression. These findings provide the basis for a potentially successful implementation of conditioning paradigms as supportive therapy to immunopharmacological regimens in clinical settings. The aim is to reduce the required amount of medication while maximizing the therapeutic outcome for the patient's benefit. [ABSTRACT FROM AUTHOR]

The prefrontal cortex and its connections with other cortical areas participate in processing erotic stimuli and hence sexual arousal. Visual erotic stimuli elicit sexual arousal that is associated with changes in electroencephalographic activity. The electroencephalographic correlation analysis provides information on the functional synchronization among areas. This study analyzed the functional interaction among the prefrontal, parietal, and temporal cortices during sexual arousal in young men induced by observing erotic photographs. In 2 groups of heterosexual men--an erotic stimulation group and a neutral stimulation group--the authors recorded electroencephalograms at the F3, F4, T3, T4, P3, and P4 derivations under 2 conditions: baseline and visual stimulation. Heart rate was monitored as a measure of peripheral activation. Participants in the erotic stimulation group reported a moderate degree of sexual arousal and a decrease in heart rate. Decreased inter- and intrahemispheric correlations of the fast frequencies were obtained only in erotic stimulation. These data support differential hemisphere participation in modulating sexual arousal and show that decreased synchronization patterns between prefrontal and posterior cortices (parietal and temporal) favor sexual arousal in young men. The results of this study may contribute to a better understanding of the central nervous system's mechanisms that underlie sexual arousal. [ABSTRACT FROM AUTHOR]

Despite host defense against parasites and pathogens being considered a costly life-history trait, relatively few studies have assessed the energetic cost of immune responsiveness. Knowledge of such energetic costs may help to understand the mechanisms by which trade-offs with other demanding activities occur. The time course and associated metabolic costs of mounting a primary and secondary humoral immune response was examined in little ringed plovers Charadrius dubius challenged with sheep red blood cells. As was expected, the injection with this antigen increased the production of specific antibodies significantly, with peaks 6 d postinjection in both primary and secondary responses. At the peak of secondary antibody response, the antibody production was 29% higher than that observed during the primary response, but the difference was nonsignificant. Mounting the primary response did not significantly increase the resting metabolic rate (RMR) of birds, whereas the secondary response did by 21%, suggesting that the latter was more costly in terms of RMR. In spite of the fact that the primary response did not involve an increase in RMR, birds significantly decreased their body mass. This could imply an internal energy reallocation strategy to cope with the induced immune challenge. Last, we found that RMR and antibody production peaks were not coupled, which could help to conciliate the variable results of previous studies. Collectively, the results of this study support the hypothesis that humoral immunity, especially the secondary response, entails energetic costs that may trade-off with other physiological activities. [ABSTRACT FROM AUTHOR]

A motivational model of gambling participation is presented. The model comprises five motivational dimensions: the dream of hitting the jackpot and transforming one's life, social rewards, intellectual challenge, mood change induced by playing, and – the fundamental motive for all gambling – the chance of winning. The model is primarily applicable to leisure gambling in contemporary western societies, but also helps us understand problem gambling. The model integrates the wide variety of motives individuals have for gambling and makes it possible to understand the specific appeal of gambling relative to other leisure activities. Gambling taps into human biopsychology, easily evokes powerful psychological processes, and connects with profound cultural meanings. [ABSTRACT FROM AUTHOR]

Brody, Costa and Hess (2012) have produced a critique containing errors both of commission and omission of my editorial (Levin 2012a) and review (Levin 2012b). This reply identifies a number of these and makes the appropriate rebuttals and vindications to correct both. [ABSTRACT FROM AUTHOR]

Large interindividual differences exist in the presence and extent of placebo responses in both experimental and clinical studies, but little is known about possible predictors of these responses. We employed a behaviorally conditioned immunosuppression paradigm in healthy men to analyze predictors of learned placebo responses. During acquisition, the subjects received either the immunosuppressant cyclosporin A (n = 32) or a placebo (n = 14) (unconditioned stimuli (US)) together with a novel-tasting drink (conditioned stimulus (CS)). During evocation, the subjects were reexposed to the CS alone. In responders (n = 15), the CS alone caused a significant inhibition of interleukin (IL)-2 production by anti-CD3-stimulated peripheral blood T cells, closely mimicking the drug effect. Nonresponders (n = 17) did not show responses different from those of the controls. Multiple-regression analyses showed that baseline IL-2, plasma noradrenaline, and state anxiety predicted nearly 60% of the variance in the conditioned IL-2 response. These data provide first evidence for putative biological and psychological predictors of learned placebo responses. [ABSTRACT FROM AUTHOR]

Orgasm is assumed to be the height of sexual pleasure, reinforcing the recurrence of sexual behaviors. Surprisingly, data supporting the role of orgasm as a reward in women appear lacking. The most likely psychological function of orgasm in women, consistent with the very limited empirical information, is as a secondary reinforcer. In other words, sexual arousal is the primary reward for sexual behavior in women and orgasm associates sexual arousal with the partner. Data from a small (n = 38 women) pilot are presented to highlight the challenges of studying female orgasm. Challenges include differentiating vaginally- or clitorally-generated orgasms by self-report and the large proportion of women who are unsure if they experience orgasms. Finally, the recent spate of publications purporting to show differences in penile-vaginal intercourse induced orgasms is critiqued in light of the information reviewed. [ABSTRACT FROM PUBLISHER]