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Nutrients Jun 2024Liver-expressed antimicrobial peptide-2 (LEAP-2) has mutual antagonism with ghrelin, which evokes food intake under a freely fed state. Nevertheless, the impact of...
Liver-expressed antimicrobial peptide-2 (LEAP-2) has mutual antagonism with ghrelin, which evokes food intake under a freely fed state. Nevertheless, the impact of LEAP-2 on ghrelin under time-restricted feeding (TRF), which has benefits in the context of metabolic disease, is still unknown. This study aims to explore the impact of central administration of LEAP-2 on the ingestion behavior of rats, which was evaluated using their cumulative food intake in the TRF state. Before intracerebroventricular (ICV) administration of -octanoylated ghrelin (0.1 nmol/rat), as a food-stimulatory model, the rats received various doses of LEAP-2 (0.3, 1, 3 nmol/rat, ICV). Cumulative food intake was recorded at 1, 2, 4, 8, 12, and 24 h after ICV injection under 12 h freely fed and TRF states in a light phase. In 12 h freely fed and TRF states, central administration of ghrelin alone induced feeding behavior. Pre-treatment with LEAP-2 (1 and 3 nmol/rat, ICV) suppressed ghrelin-induced food intake in a dose-dependent manner in a 12 h freely fed state instead of a TRF state, which may have disturbed the balance of ghrelin and LEAP-2. This study provides neuroendocrine-based evidence that may explain why TRF sometimes fails in fighting obesity/metabolic dysfunction-associated steatotic liver disease in clinics.
Topics: Animals; Ghrelin; Male; Rats; Eating; Feeding Behavior; Injections, Intraventricular; Antimicrobial Cationic Peptides; Rats, Sprague-Dawley; Consciousness; Blood Proteins
PubMed: 38931301
DOI: 10.3390/nu16121946 -
Nutrients Jun 2024Breast cancer is the most common tumor in women. Chemotherapy is the gold standard for cancer treatment; however, severe side effects and tumor resistance are the major... (Review)
Review
Breast cancer is the most common tumor in women. Chemotherapy is the gold standard for cancer treatment; however, severe side effects and tumor resistance are the major obstacles to chemotherapy success. Numerous dietary components and phytochemicals have been found to inhibit the molecular and signaling pathways associated with different stages of breast cancer development. In particular, this review is focused on the antitumor effects of PUFAs, dietary enzymes, and glucosinolates against breast cancer. The major databases were consulted to search in vitro and preclinical studies; only those with solid scientific evidence and reporting protective effects on breast cancer treatment were included. A consistent number of studies highlighted that dietary components and phytochemicals can have remarkable therapeutic effects as single agents or in combination with other anticancer agents, administered at different concentrations and via different routes of administration. These provide a natural strategy for chemoprevention, reduce the risk of breast cancer recurrence, impair cell proliferation and viability, and induce apoptosis. Some of these bioactive compounds of dietary origin, however, show poor solubility and low bioavailability; hence, encapsulation in nanoformulations are promising tools able to increase clinical efficiency.
Topics: Humans; Breast Neoplasms; Female; Phytochemicals; Diet; Chemoprevention; Drug Synergism; Animals; Antineoplastic Combined Chemotherapy Protocols; Glucosinolates
PubMed: 38931238
DOI: 10.3390/nu16121883 -
Medicina (Kaunas, Lithuania) Jun 2024This study aimed to identify the effectiveness and potential complications on the harvest site and knee of bone marrow aspirate concentrate (BMAC) treatment of patients...
This study aimed to identify the effectiveness and potential complications on the harvest site and knee of bone marrow aspirate concentrate (BMAC) treatment of patients with Kellgren-Lawrence (K-L) grades II-III knee osteoarthritis (OA) over a minimum follow-up period of 6 months. This study retrospectively evaluated data from 231 patients (285 knees) with knee OA treated with BMAC articular injection at a single center from August 2023 to October 2023. The inclusion criteria were a longstanding knee pain unresponsive to conservative treatments for at least 6 weeks with K-L grades II-III OA. The exclusion criteria were age of <40 years or >80 years, previous knee surgery, rheumatological or other systemic disease, malignancy, uncontrolled diabetes mellitus, or infections. Bone marrow was aspirated from the anterior iliac crest and concentrated by the single-spin centrifugation technique. The visual analog scale (VAS) pain score and Knee Society Score were used to evaluate the clinical outcomes and complications associated with harvest and injection sites were evaluated. The mean follow-up period was 7.2 months (range: 6-8 months). The pretreatment VAS pain score decreased from 4.3 to 0.4 points at the final follow-up ( < 0.05). Pretreatment Knee Society knee and function scores were improved from 86.9 to 98.1 ( < 0.05) and from 68.4 to 83.3 points ( < 0.05), respectively. A total of 15 complications (5.3%, 15/285) were observed, including 3 hematomas, 2 numbness, 2 contact dermatitis, and 1 superficial infection in the harvest site and 4 mild and moderate swelling and 3 severe swelling and pain in the injection site. BMAC is a reliable and effective treatment for patients with K-L grades II-III knee OA, but the orthopedic surgeon should consider that bleeding tendency by heparin causes severe joint swelling and pain after intra-articular knee injection.
Topics: Humans; Osteoarthritis, Knee; Male; Female; Middle Aged; Retrospective Studies; Aged; Treatment Outcome; Adult; Pain Measurement; Bone Marrow Transplantation; Injections, Intra-Articular; Aged, 80 and over
PubMed: 38929594
DOI: 10.3390/medicina60060977 -
Medicina (Kaunas, Lithuania) Jun 2024The prolonged infusion of meropenem is recommended by guidelines for the treatment of sepsis. However, studies provide controversial data on the advantages of prolonged...
The prolonged infusion of meropenem is recommended by guidelines for the treatment of sepsis. However, studies provide controversial data on the advantages of prolonged infusions over intermittent ones. In our opinion, this can be related to age, which possibly distorts the final data, as older people have age-related characteristics. In our study, we analyzed the ventilatory status, laboratory tests and vital signs of the patient and carried out microbiological cultures. This was a prospective single-center case series investigation conducted from June 2022 to June 2023. The objective of this study was to evaluate the effectiveness of continuous infusion in elderly patients with severe infectious complications after orthopedic interventions. The primary endpoints were 28-day survival and the emergence of new multidrug-resistant strains. Secondary endpoints were long-term mortality and length of stay in the ICU. : Three patients (median age 65, 100% female) received a continuous infusion of meropenem. Two patients were alive at hospital discharge, and one patient died on the 105th day of hospitalization. Multi-resistant bacteria were observed in one patient. The use of a continuous meropenem infusion in the complex treatment of purulent-septic complications in elderly patients with periprosthetic infection and anemia probably led to clinical improvement in these case reports. However, the emergence of new pan-resistant strains and overall mortality using this infusion technique remains unclear. Further, high-quality RCTs for the elderly are needed.
Topics: Humans; Meropenem; Aged; Female; Anti-Bacterial Agents; Prospective Studies; Male; Anemia; Infusions, Intravenous; Middle Aged; Aged, 80 and over; Sepsis
PubMed: 38929546
DOI: 10.3390/medicina60060929 -
Medicina (Kaunas, Lithuania) May 2024: Inadequate treatment of asthma and chronic obstructive pulmonary disease (COPD) might have a negative impact on their progression. Inhalation therapy is the...
: Inadequate treatment of asthma and chronic obstructive pulmonary disease (COPD) might have a negative impact on their progression. Inhalation therapy is the cornerstone of pharmacotherapy for these conditions. However, challenges such as low adherence, negative attitudes, and misconceptions about inhaled medications still persist, impeding effective disease management. This study aimed to evaluate adherence, ascertain the level of disease control in asthma and COPD, explore potential misconceptions surrounding inhalation therapy among patients with obstructive lung diseases and the general population in Vojvodina, and evaluate the reliability of newly developed questionnaires employed in the study. : This cross-sectional study utilized a battery of questionnaires encompassing sociodemographic data, the Asthma Control Test (ACT), the COPD Assessment Test (CAT), along with two novel questionnaires-one for assessing adherence and another for analyzing attitudes toward inhalation therapy. Statistical analyses were conducted using SPSS software, version 25.0. : The average ACT score among patients with asthma was 17.31, while it was 19.09 for the CAT questionnaire among COPD patients. The composite score on the newly developed adherence assessment questionnaire was 2.27, exhibiting a reliability coefficient lower than recommended (α = 0.468). Significant statistical differences emerged among sample subgroups regarding attitudes and misconceptions toward inhalation therapy. The reliability coefficient for this questionnaire was deemed satisfactory (α = 0.767). : Adherence rates were notably suboptimal in both subgroups of the studied population. The disease control levels were higher among asthma patients, while they exhibited less prevalent misconceptions regarding inhalation therapy compared to COPD patients and the healthy population.
Topics: Humans; Cross-Sectional Studies; Male; Female; Middle Aged; Surveys and Questionnaires; Pulmonary Disease, Chronic Obstructive; Adult; Administration, Inhalation; Aged; Medication Adherence; Asthma; Respiratory Therapy; Reproducibility of Results
PubMed: 38929470
DOI: 10.3390/medicina60060853 -
International Journal of Molecular... Jun 2024The gold standard in the non-surgical treatment of periodontitis is scaling and root planing (SRP). In recent years, the use of autogenous platelet concentrates has... (Review)
Review
The gold standard in the non-surgical treatment of periodontitis is scaling and root planing (SRP). In recent years, the use of autogenous platelet concentrates has spread over many specialties in dentistry and, thus, has also been gaining popularity in periodontal treatment. Its two main fractions are platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), which, since 2014, can also be used via injection as injectable platelet-rich fibrin (i-PRF). The authors conducted a comprehensive systematic review in accordance with the PRISMA 2020 guidelines. It involved searching PubMed, Embase, Scopus, and Google Scholar databases using the phrases ("Root Planing" OR "Subgingival Curettage" OR "Periodontal Debridement") AND ("Platelet-Rich Plasma"). Based on the authors' inclusion and exclusion criteria, 12 results were included in the review, out of 1170 total results. The objective of this review was to ascertain the impact of utilizing PRP and i-PRF in SRP. The results revealed that both the incorporation of PRP and i-PRF were found to be significantly associated with are duction in gingival pocket depth and again in clinical attachment level; however, i-PRF demonstrated superiority in improving clinical parameters. Furthermore, i-PRF demonstrated notable bactericidal efficacy against . On the other hand, PRP proved inferior to an Nd:YAG laser in clinical parameter improvement; however, it demonstrated significant efficiency as well. This literature review led the authors to the conclusion that autologous platelet concentrates might be competent agents for improving the therapeutic outcomes of SRP.
Topics: Humans; Platelet-Rich Plasma; Platelet-Rich Fibrin; Periodontitis; Root Planing; Injections
PubMed: 38928026
DOI: 10.3390/ijms25126319 -
International Journal of Molecular... Jun 2024Noise-induced hearing loss (NIHL) is a major cause of hearing impairment and is linked to dementia and mental health conditions, yet no FDA-approved drugs exist to...
Noise-induced hearing loss (NIHL) is a major cause of hearing impairment and is linked to dementia and mental health conditions, yet no FDA-approved drugs exist to prevent it. Downregulating the mitogen-activated protein kinase (MAPK) cellular pathway has emerged as a promising approach to attenuate NIHL, but the molecular targets and the mechanism of protection are not fully understood. Here, we tested specifically the role of the kinases ERK1/2 in noise otoprotection using a newly developed, highly specific ERK1/2 inhibitor, tizaterkib, in preclinical animal models. Tizaterkib is currently being tested in phase 1 clinical trials for cancer treatment and has high oral bioavailability and low predicted systemic toxicity in mice and humans. In this study, we performed dose-response measurements of tizaterkib's efficacy against permanent NIHL in adult FVB/NJ mice, and its minimum effective dose (0.5 mg/kg/bw), therapeutic index (>50), and window of opportunity (<48 h) were determined. The drug, administered orally twice daily for 3 days, 24 h after 2 h of 100 dB or 106 dB SPL noise exposure, at a dose equivalent to what is prescribed currently for humans in clinical trials, conferred an average protection of 20-25 dB SPL in both female and male mice. The drug shielded mice from the noise-induced synaptic damage which occurs following loud noise exposure. Equally interesting, tizaterkib was shown to decrease the number of CD45- and CD68-positive immune cells in the mouse cochlea following noise exposure. This study suggests that repurposing tizaterkib and the ERK1/2 kinases' inhibition could be a promising strategy for the treatment of NIHL.
Topics: Animals; Mice; Administration, Oral; Hearing Loss, Noise-Induced; Male; Protein Kinase Inhibitors; MAP Kinase Signaling System; Female; Disease Models, Animal; Cochlea
PubMed: 38928015
DOI: 10.3390/ijms25126305 -
Biomolecules May 2024Mesenchymal stem/stromal cell-derived small extracellular vesicles (MSC-sEVs) are promising therapeutic agents. In this study, we investigated how the administration...
Mesenchymal stem/stromal cell-derived small extracellular vesicles (MSC-sEVs) are promising therapeutic agents. In this study, we investigated how the administration route of MSC-sEVs affects their therapeutic efficacy in a mouse model of bleomycin (BLM)-induced skin scleroderma (SSc). We evaluated the impact of topical (TOP), subcutaneous (SC), and intraperitoneal (IP) administration of MSC-sEVs on dermal fibrosis, collagen density, and thickness. All three routes of administration significantly reduced BLM-induced fibrosis in the skin, as determined by Masson's Trichrome staining. However, only TOP administration reduced BLM-induced dermal collagen density, with no effect on dermal thickness observed for all administration routes. Moreover, SC, but not TOP or IP administration, increased anti-inflammatory profibrotic CD163 M2 macrophages. These findings indicate that the administration route influences the therapeutic efficacy of MSC-sEVs in alleviating dermal fibrosis, with TOP administration being the most effective, and this efficacy is not mediated by M2 macrophages. Since both TOP and SC administration target the skin, the difference in their efficacy likely stems from variations in MSC-sEV delivery in the skin. Fluorescence-labelled TOP, but not SC MSC-sEVs when applied to skin explant cultures, localized in the stratum corneum. Hence, the superior efficacy of TOP over SC MSC-sEVs could be attributed to this localization. A comparison of the proteomes of stratum corneum and MSC-sEVs revealed the presence of >100 common proteins. Most of these proteins, such as filaggrin, were known to be crucial for maintaining skin barrier function against irritants and toxins, thereby mitigating inflammation-induced fibrosis. Therefore, the superior efficacy of TOP MSC-sEVs over SC and IP MSC-sEVs against SSc is mediated by the delivery of proteins to the stratum corneum to reinforce the skin barrier.
Topics: Animals; Mesenchymal Stem Cells; Mice; Bleomycin; Extracellular Vesicles; Skin; Disease Models, Animal; Fibrosis; Female; Filaggrin Proteins; Macrophages; Drug Administration Routes; Humans
PubMed: 38927026
DOI: 10.3390/biom14060622 -
BMC Veterinary Research Jun 2024The present study was performed to characterize and compare the perfusion of vaginal and uterine arteries after challenging the reproductive tract of dairy cows via...
AIM
The present study was performed to characterize and compare the perfusion of vaginal and uterine arteries after challenging the reproductive tract of dairy cows via natural mating, artificial insemination (AI), or intravaginal deposition (vaginal fundus) of different biological fluids or a placebo.
MATERIALS AND METHODS
In a double-blind study, six German Holstein cows were administered PGF during dioestrus and 48 h later treated with GnRH. Intravaginal or intrauterine treatments were carried out 12 h after GnRH was administered. Animals served as their controls, using a cross-over design with an interval of 14 days between experiments. The experimental animals were allocated to receive the following treatments: natural mating (N), intrauterine artificial insemination (A), intravaginal deposition (vaginal fundus) of 6 mL raw semen (R) or 6 mL seminal plasma (S), and compared to their controls [control 1: 6 mL placebo (P: physiological saline); control 2: no treatment (C)). Corresponding time intervals were chosen for the untreated control oestrus. Blood flow volume (BFV) in the uterine (u) and vaginal (v) arteries ipsilateral to the ovary bearing the preovulatory follicle was determined using transrectal Doppler sonography.
RESULTS
All animals exhibited oestrus and ovulated between 30 and 36 h after GnRH. Transient increases (P < 0.05) in vaginal blood flow occurred between 3 and 12 h following mating as well as 3 to 9 h after deposition of raw semen and seminal plasma, respectively. The most distinct increases (199%) in vBFV occurred 6 h after mating compared to values immediately before mating (= time 0 h). Neither AI nor deposition of a placebo into the vagina affected vBFV (P > 0.05). Only mating and deposition of either raw semen, seminal plasma or AI increased uBFV (P < 0.003). The greatest rise in uBFV occurred after natural mating. Maximum uBFV values were detected 9 h after mating when values were 79% greater (P < 0.05) than at 0 h.
CONCLUSIONS
The natural mating, deposition of raw semen or seminal plasma and conventional AI affect vaginal and/or uterine blood flow to different degrees. The factors responsible for these alterations in blood flow and their effects on fertility remain to be clarified in future studies.
Topics: Animals; Insemination, Artificial; Female; Semen; Cattle; Vagina; Uterus; Male; Administration, Intravaginal; Double-Blind Method; Gonadotropin-Releasing Hormone; Cross-Over Studies; Regional Blood Flow
PubMed: 38926710
DOI: 10.1186/s12917-024-03919-x -
Scientific Reports Jun 2024To compare the efficacy and safety of the proposed aflibercept biosimilar SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration,... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
To compare the efficacy and safety of the proposed aflibercept biosimilar SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration, this randomized, double-masked, parallel-group, multicenter study was conducted in 14 countries from 13 August 2020 to 8 September 2022. Patients with neovascular age-related macular degeneration. With subfoveal, juxtafoveal, or extrafoveal choroidal neovascularization were aged 50 years or older. Intravitreal injection of SCD411 or aflibercept (2.0 mg) were administered every 4 weeks for the first three injections and every 8 weeks until week 48. The primary efficacy endpoint was the change in best-corrected visual acuity from baseline to week 8 with an adjusted equivalence margin of ± 3.0 letters. Patients were randomly assigned to receive either SCD411 (n = 288) or reference aflibercept (n = 288). A total of 566 participants (98.3%) completed week 8 of the study. The least-squares mean difference of change in best-corrected visual acuity from baseline to week 8 (SCD411-aflibercept) was - 0.4 letters (90% confidence interval = - 1.6 to 0.9). The incidence of ocular (69 of 287 [24.0%] vs. 71 of 286 [24.8%]) and serious ocular (5 of 287 [1.7%] vs. 3 of 286 [1.0%]) treatment-emergent adverse effects were similar between the SCD411 and aflibercept groups. Immunogenicity analysis revealed a low incidence of neutralizing antibody formation in both groups. In conclusion, SCD411 has equivalent efficacy compared with reference aflibercept in patients with neovascular age-related macular degeneration and has a comparable safety profile. The results support the potential use of SCD411 for the treatment of neovascular age-related macular degeneration.
Topics: Humans; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Male; Female; Aged; Visual Acuity; Intravitreal Injections; Treatment Outcome; Macular Degeneration; Middle Aged; Double-Blind Method; Aged, 80 and over; Choroidal Neovascularization; Biosimilar Pharmaceuticals; Angiogenesis Inhibitors
PubMed: 38926553
DOI: 10.1038/s41598-024-65815-6