The low response rate of current cancer immunotherapy suggests the presence of few antigen-specific T cells and a high number of immunosuppressive factors in tumor microenvironment (TME). Here, we ...develop a syringeable immunomodulatory multidomain nanogel (iGel) that overcomes the limitation by reprogramming of the pro-tumoral TME to antitumoral immune niches. Local and extended release of immunomodulatory drugs from iGel deplete immunosuppressive cells, while inducing immunogenic cell death and increased immunogenicity. When iGel is applied as a local postsurgical treatment, both systemic antitumor immunity and a memory T cell response are generated, and the recurrence and metastasis of tumors to lungs and other organs are significantly inhibited. Reshaping of the TME using iGel also reverts non-responding groups to checkpoint blockade therapies into responding groups. The iGel is expected as an immunotherapeutic platform that can reshape immunosuppressive TMEs and synergize cancer immunotherapy with checkpoint therapies, with minimized systemic toxicity.
Background
Ruminococcus gnavus (R. gnavus) are mucin‐degrading gut bacteria that play a key role in the early colonization of the gut by serving as endogenous sources of nutrients. They can also ...influence immune development. We had previously reported a lower abundance of R. gnavus in infants with atopic dermatitis (AD) compared with that in healthy subjects. However, the underlying mechanisms remain unclear. In this study, we investigated the effect of orally administered R. gnavus on antibiotic treatment‐induced gut dysbiosis (and the underlying mechanism) in a mouse model of AD.
Methods
Four‐week‐old female BALB/C mice were administered antibiotic cocktails for 2 weeks. R. gnavus was orally administered throughout the study duration. At 6 weeks of age, AD was induced by epidermal sensitization with ovalbumin. AD phenotypes and systemic and gut immune responses were investigated.
Results
Orally administered R. gnavus significantly reduced AD‐associated parameters (i.e., transepidermal water loss, clinical score, total serum immunoglobulin (Ig) E level, OVA‐specific IgE level, and skin inflammation). R. gnavus treatment also resulted in significant downregulation of T helper 2–related cytokine mRNA and upregulation of interleukin (IL)‐10 and Foxp3 in the skin. The population of CD4+FOXP3+ T cells in mesenteric‐ and skin‐draining lymph nodes and butyrate levels in the cecum increased in R. gnavus‐administered AD mice.
Conclusions
Immune modulation by orally administered R. gnavus may alleviate AD symptoms through the enhancement of regulatory T‐cell counts and short‐chain fatty acids production in AD mice.
Development of sensing technology with wearable chemical sensors is realizing non-invasive, real-time monitoring healthcare and disease diagnostics. The advanced sensor devices should be compact and ...portable for use in limited space, easy to wear on human body, and low-cost for personalized healthcare markets. Here, we report a highly sensitive, flexible, and autonomously self-healable pH sensor cable developed by weaving together two carbon fiber thread electrodes coated with mechanically robust self-healing polymers. The pH sensor cable showed excellent electrochemical performances of sensitivity, repeatability, and durability. Spontaneous and autonomous sensor healing efficiency of the pH sensor cable was demonstrated by measuring sensitivity during four cycles of cutting and healing process. The pH sensor cable could measure pH in small volumes of real human fluid samples, including urine, saliva, and sweat, and the results were similar to those of a commercial pH meter. Taken together, successful real-time pH monitoring for human sweat was demonstrated by fabricating a wearable sensing system in which the pH sensor cable was knitted into a headband integrated with wireless electronics.
•A robust and self-healing polymer was synthesized from biomass-derived and non-toxic monomers.•pH sensor cables fabricated by weaving two carbon fiber thread electrodes showed excellent potentimetric performances.•A remarkable self-healing efficiency for sensitivity of pH sensor cables with a short healing time.•Real-time monitoring capabilities of pH sensor cables for real human fluids of tear, urine, saliva, and sweat.
To identify oseltamivir resistance, we analyzed neuraminidase H275Y mutations in samples from 10 patients infected with pandemic (H1N1) 2009 virus in South Korea who had influenza that was refractory ...to antiviral treatment with this drug. A neuraminidase I117M mutation that might influence oseltamivir susceptibility was detected in sequential specimens from 1 patient.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Standard treatments for gynecological cancers include surgery, chemotherapy, and radiation therapy. However, there are limitations associated with the chemotherapeutic drugs used to treat advanced ...and recurrent gynecological cancers, and it is difficult to identify additional treatments. Therefore, immune checkpoint inhibitor (ICI) therapy products, including PD-1/PD-L1 inhibitors and CTLA-4 inhibitors, are in the spotlight as alternatives for the treatment of advanced gynecological cancers. Although the ICI monotherapy response rate in gynecological cancers is lower than that in melanoma or non-small cell lung cancer, the response rates are approximately 13-52%, 7-22%, and 4-17% for endometrial, ovarian, and cervical cancers, respectively. Several studies are being conducted to compare the outcomes of combining ICI therapy with chemotherapy, radiation therapy, and antiangiogenesis agents. Therefore, it is critical to determine the mechanism underlying ICI therapy-mediated anti-tumor activity and its application in gynecological cancers. Additionally, understanding the possible immune-related adverse events induced post-immunotherapy, as well as the appropriate management of diagnosis and treatment, are necessary to create a quality environment for immunotherapy in patients with gynecological cancers. Therefore, in this review, we summarize the ICI mechanisms, ICIs applied to gynecological cancers, and appropriate diagnosis and treatment of immune-related side effects to help gynecologists treat gynecological cancers using immunotherapy.
Sensors with autonomous self-healing properties offer enhanced durability, reliability, and stability. Although numerous self-healing polymers have been attempted, achieving sensors with fast and ...reversible recovery under ambient conditions with high mechanical toughness remains challenging. Here, a highly sensitive wearable sensor made of a robust bio-based supramolecular polymer that is capable of self-healing via hydrogen bonding is presented. The integration of carbon fiber thread into a self-healing polymer matrix provides a new toolset that can easily be knitted into textile items to fabricate wearable sensors that show impressive self-healing efficiency (>97.0%) after 30 s at room temperature for K+/Na+ sensing. The wearable sweat-sensor systemcoupled with a wireless electronic circuit board capable of transferring data to a smart phonesuccessfully monitors electrolyte ions in human perspiration noninvasively in real time, even in the healed state during indoor exercise. Our smart sensors represent an important advance toward futuristic personalized healthcare applications.
Peritoneal fibrosis (PF) is an intractable complication of peritoneal dialysis (PD) that leads to peritoneal membrane failure. This study investigated the role of suppression of tumorigenicity (ST)2 ...in PF using patient samples along with mouse and cell‐based models. Baseline dialysate soluble (s)ST2 level in patients measured 1 month after PD initiation was 2063.4 ± 2457.8 pg/mL; patients who switched to haemodialysis had elevated sST2 levels in peritoneal effluent (1576.2 ± 199.9 pg/mL, P = .03), which was associated with PD failure (P = .04). Baseline sST2 showed good performance in predicting PD failure (area under the receiver operating characteristic curve = 0.780, P = .001). In mice with chlorhexidine gluconate‐induced PF, ST2 was expressed in fibroblasts and mesothelial cells within submesothelial zones. In primary cultured human peritoneal mesothelial cells (HPMCs), transforming growth factor‐β treatment increased ST2, fibronectin, β‐galactosidase and Snail protein levels and decreased E‐cadherin level. Anti‐ST2 antibody administration reversed the up‐regulation of ST2 and fibronectin expression; it also reduced fibrosis induced by high glucose (100 mmol/L) in HPMCs. Thus, high ST2 level in dialysate is a marker for fibrosis and inflammation during peritoneal injury, and blocking ST2 may be an effective therapeutic strategy for renal preservation.
This study analyzed 5322 camera trap photographs from Halla Mountain Wetland, documenting 1427 independent bird sightings of 26 families and 49 species of Passeriformes. Key observations include ...morning activities in
and
and afternoon activity in
and
. Wetlands were significantly preferred (P_i = 0.398) despite their smaller area, contrasting with underutilized grasslands (P_i = 0.181). Seasonal activity variations were notable, with overlap coefficients ranging from 0.08 to 0.81 across species, indicating diverse strategies in resource utilization and thermoregulation. Population density was found to be a critical factor in habitat usage, with high-density species showing more consistent activity patterns. The study's results demonstrate the ecological adaptability of Passeriformes in the Halla Mountain Wetland while highlighting the limitations of camera trapping methods. These limitations include their fixed field of view and intermittent recording capability, which may not fully capture the spectrum of complex avian behaviors. This research underlines the need for future studies integrating various methodologies, such as direct observation and acoustic monitoring, to gain a more comprehensive understanding of avian ecology.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Prolintane (1-Phenyl-2-pyrrolidinylpentane), a synthetic central nervous system (CNS) stimulant, is structurally similar to amphetamine but pharmacologically acts as a dopamine reuptake inhibitor ...like cocaine. While several case studies reported adverse effects and recreational use of prolintane, the abuse potential of the drug has not been systemically examined yet. In the present study, we evaluated the behavioral effects of prolintane regarding its abuse liability in rodents using locomotor activity, conditioned place preference (CPP), self-administration (SA), and drug discrimination paradigms, as well as in-vivo microdialysis experiment. First, acute prolintane (10 and 20 mg/kg, intraperitoneal injection) increased locomotor activity (distance traveled, cm) in mice but to a lesser degree than methamphetamine (as a positive control). We also found that a single and solitary injection of prolintane (20 mg/kg, IP) significantly increased extracellular dopamine in the striatum. The following result suggests that its stimulatory effects might be associated with the mesolimbic dopaminergic pathway. Further, prolintane produced a significant drug-paired place preference at doses of both 10 and 20 mg/kg. In the SA experiment, the mice that self-administered prolintane intravenously (4 mg/kg/inf) showed a higher infusion and active lever responses but not inactive lever responses. Additionally, cumulative doses of prolintane partially elicited cocaine-appropriate lever responses (38.57% at doses up to 10 mg/kg) in rats. These results implied that prolintane has not only rewarding and reinforcing effects but also interoceptive stimulus properties, which are similar to cocaine at a moderate level. Taken together, this study was the first to show, to our knowledge, that prolintane has a certain level of abuse potential and should be considered carefully as a valuable basis for legal restrictions on use.
This article is part of the special Issue on ‘Stress, Addiction and Plasticity'.
•Prolintane increases locomotor activity in mice in a lesser degree than methamphetamine.•Single injection of prolintane results a significant increase in extracellular dopamine in the striatum.•Prolintane produces a significant drug-paired place preference in mice.•Prolintane leads to a greater number of infusion and active lever responses in self-administration of mice.•Prolintane produces partial substitution for cocaine in rats.
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