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15 pages, 997 KB  
Article
Effects of Menstrual Phases on Cardiovascular and Autonomic Responses to ISS-Themed Virtual Reality Environment in Supine and Standing Postures: A Pilot Study
by Hamda Mahboub, Mariam Alnaqbi, Maryam Yateem, Anova Elizabeth Sebastian, Malik Nasir Afzal Khan, Salonaz Abdelglil, Najma Mohamed Ali, Suhaila Alnuaimi, Fatima Ahmed Al Marzouqi, Mohammad Yousuf Bin Nashooq, Shaikha Ahmad Al Falasi, Hanan Alsuwaidi and Nandu Goswami
Physiologia 2026, 6(3), 50; https://doi.org/10.3390/physiologia6030050 - 6 Aug 2026
Viewed by 199
Abstract
Background: Changes in estrogen and progesterone during the menstrual cycle could potentially influence standing-induced hemodynamic and autonomic responses. Aims and Objectives: We aimed to explore the effects of menstrual cycle phases on cardiovascular and autonomic adaptations to a virtual reality International [...] Read more.
Background: Changes in estrogen and progesterone during the menstrual cycle could potentially influence standing-induced hemodynamic and autonomic responses. Aims and Objectives: We aimed to explore the effects of menstrual cycle phases on cardiovascular and autonomic adaptations to a virtual reality International Space Station (ISS) environment used as a microgravity analogue across varying body positions. Method: A randomized repeated-measures pilot study was conducted with two protocols (supine and standing) in an International Space Station-themed virtual reality environment involving healthy young female (n = 11, mean age 20 ± 1 years, height 160.6 ± 3 cm, weight 61.6 ± 9 kg) participants in 2 menstrual phases: follicular (n = 5, 20 ± 1 years, height 160 ± 3 cm, weight 55 ± 6 kg) and luteal phase (n = 6, mean age 20 ± 1 years, height 161.3 ± 2.4 cm, weight 67 ± 8 kg). Each protocol consisted of three stages: baseline, supine/standing, and recovery, each lasting 5 min. The data were analyzed using mixed repeated-measures analysis of variance. Results: Significant differences were observed between the two protocols from supine to standing across menstrual phases for several hemodynamic variables. Heart rate showed significant difference during the luteal phase (F(1,9) = 10.6, p = 0.01) with values from 72 bpm to 84 bpm and the follicular phase (F(1,9) = 7.4, p = 0.02) from 82 bpm to 92 bpm; diastolic blood pressure during the follicular phase (F(1,9) = 9.8, p = 0.01) from 55 mmHg to 80 mmHg; mean arterial pressure during the follicular phase (F(1,9) = 7.5, p = 0.02) from 73 mmHg to 93 mmHg; stroke index during the follicular phase (F(1,9) = 6.9, p = 0.03) from 74 mL/m2 to 51 mL/m2; and systemic vascular resistance index during the follicular phase (F(1,9) = 8.0, p = 0.02), with values from 1046 dyn*sec* m2/cm5 to 1564 dyn*sec* m2/cm5, respectively. This was a preliminary pilot study, and the results need to be confirmed with larger groups and validated hormonally. Conclusions: These exploratory pilot study results show that orthostatic-induced responses are influenced by the menstrual cycle phase. Since no non-VR control condition was included, the responses observed should be considered part of the VR-based protocol, and the exact role of the immersive virtual reality environment cannot be determined. The study showed that an ISS-themed virtual reality environment led to notable changes in cardiovascular function and autonomic responses during transitions from supine to standing postures, and these responses also varied across menstrual phases. Across most epochs, the standing protocol consistently shows higher heart rate, systolic and diastolic blood pressure, mean arterial pressure, and systemic vascular resistance index than the supine protocol, reflecting the effect of orthostatic loading in an ISS-themed virtual reality environment. Full article
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26 pages, 740 KB  
Article
The Influence of Serum Iron Levels on Depression, Anxiety, Fatigue, Neuropathic Pain and MR Disease Activity in Patients with Multiple Sclerosis
by Simonida Delic, Svetlana Miletic Drakulic, Snezana Lazarevic, Milos Stepovic, Nikoleta Janicijevic, Maja Vulovic, Aleksandra Mitrovic Zivanovic, Danica Igrutinovic, Melanija Tepavcevic, Milica Dimitrijevic, Katarina Manojlovic, Bojana Markovic, Nebojsa Igrutinovic, Vladimir Markovic and Ana Azanjac Arsic
NeuroSci 2026, 7(4), 86; https://doi.org/10.3390/neurosci7040086 - 27 Jul 2026
Viewed by 277
Abstract
Background: Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system. Our study aimed to examine the relationship between serum iron levels and the following clinical parameters: depression, anxiety, fatigue, neuropathic pain, and disease activity on magnetic [...] Read more.
Background: Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system. Our study aimed to examine the relationship between serum iron levels and the following clinical parameters: depression, anxiety, fatigue, neuropathic pain, and disease activity on magnetic resonance imaging in patients with relapsing-remitting multiple sclerosis (RRMS). Material and methods: This study was designed as a clinical observational, cross-sectional study. This study was conducted at the Clinic of Neurology of the University Clinical Center Kragujevac, from 2022 to 2024, according to the ethical code of the Declaration of Helsinki. Demographic and clinical data on patients were obtained from the medical history. All MS patients were diagnosed according to the McDonald criteria (2017). This study included 65 patients in the experimental group and 11 healthy individuals in the control group, with an average age of 39.68 years. Serum iron levels were biochemically analyzed from venous blood. The following standardized tests were used to collect data on depression, anxiety, fatigue, and neuropathic pain: Beck Depression Inventory (BDI), Hamilton Anxiety Rating Scale (HAM-A), Modified Fatigue Impact Scale (MFIS), PainDETECT Questionnaire (PD-Q), and Visual Analogue Scale (VAS). Results: Serum iron level significantly correlates with disease activity on magnetic resonance imaging in patients with multiple sclerosis. Serum iron showed a moderate positive correlation with hemoglobin, hematocrit, total and direct bilirubin, and a weak positive correlation with uric acid, while a moderate negative correlation was observed with erythrocyte sedimentation rate. No statistically significant difference was found between serum iron levels and depression, anxiety, fatigue, and severity of neuropathic pain. The ROC curves show the diagnostic potential of the combined parameters in differentiating RRMS from controls, as well as the potential of iron in differentiating active from inactive MS. The presence of disease, hemoglobin and total bilirubin were recorded as significant independent predictors. Conclusion: This study is a descriptive attempt to present the potential role of iron in the radiological activity of the disease. High serum iron level may be associated with radiological disease activity in patients with multiple sclerosis. Full article
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21 pages, 5434 KB  
Article
Cord Blood-Derived Versus Homologous Donor Platelet-Rich Plasma (PRP) in Early Knee Osteoarthritis: A Single-Center, Randomized, Double-Blind Pilot Clinical Trial
by Salvatore Alessio Angileri, Enrica Cristini, Simone Mazzola, Giovanni Maria Rodà, Chloe Yeabin Jung, Salvatore Valentino, Stefania Villa, Tiziana Montemurro, Larysa Mykhailova, Letizia Di Meglio, Simone Raoul Mortellaro, Vittoria Chiarpenello, Carolina Lanza, Roberta Gualtierotti, Daniele Prati, Gianpaolo Carrafiello and Luigi Piero Solimeno
Bioengineering 2026, 13(7), 806; https://doi.org/10.3390/bioengineering13070806 - 14 Jul 2026
Viewed by 491
Abstract
Intra-articular platelet-rich plasma (PRP) injections represent a promising biological treatment for early-stage knee osteoarthritis (KOA). As cord blood-derived PRP (CB-PRP) contains higher levels of bioactive mediators, this prospective study aimed to compare the efficacy and safety of CB-PRP versus homologous donor PRP (HD-PRP) [...] Read more.
Intra-articular platelet-rich plasma (PRP) injections represent a promising biological treatment for early-stage knee osteoarthritis (KOA). As cord blood-derived PRP (CB-PRP) contains higher levels of bioactive mediators, this prospective study aimed to compare the efficacy and safety of CB-PRP versus homologous donor PRP (HD-PRP) in patients with early KOA and to evaluate whether CB-PRP results in greater clinical improvement. Fifty-one patients aged 46–70 years with Kellgren–Lawrence grade 1–2 were randomized to receive either CB-PRP or HD-PRP. Each underwent three intra-articular injections at four-week intervals. Outcomes included pain-related overall health perception assessed by the EuroQol Visual Analogue Scale (EQ-VAS), function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS), and quadriceps muscle strength evaluated by dynamometry. Assessments were performed at baseline and at 1, 2, 3, 6, and 12 months. Both groups showed improvements in pain and function over 12 months, with no statistically significant between-group differences (p = 0.46). EQ-VAS increased from 59 ± 19 to 83 ± 9 in the CB-PRP group and from 59 ± 18 to 77 ± 18 in the HD-PRP group. KOOS improved from 50 ± 25 to 68 ± 23 and from 38 ± 28 to 59 ± 24, respectively. Quadriceps strength showed no intergroup differences. Adverse events were mild and self-limiting. Both treatments demonstrated comparable clinical benefits and favorable safety profiles. Full article
(This article belongs to the Section Regenerative Engineering)
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14 pages, 2024 KB  
Article
Percutaneous Endoscopic Interlaminar Discectomy via a Modified Inferolateral Margin of the L5 Pedicle Projection for L5/S1 Central Disc Herniation: A Retrospective Study
by Chenxing Huang, Bin Xie, Zhuangzhuang Tan, Jiajun Cheng, Xiaoteng Feng, Zhenghao Huang, Zhaojun Cheng, Gengyang Shen, Hui Ren, Jingjing Tang and Xiaobing Jiang
J. Clin. Med. 2026, 15(14), 5355; https://doi.org/10.3390/jcm15145355 - 8 Jul 2026
Viewed by 322
Abstract
Objective: To evaluate the feasibility and short-term outcomes of a modified percutaneous endoscopic interlaminar discectomy (PEID) trajectory via the inferolateral margin of the L5 pedicle projection for central disc herniation at L5/S1. Methods: From June 2023 to July 2025, a consecutive [...] Read more.
Objective: To evaluate the feasibility and short-term outcomes of a modified percutaneous endoscopic interlaminar discectomy (PEID) trajectory via the inferolateral margin of the L5 pedicle projection for central disc herniation at L5/S1. Methods: From June 2023 to July 2025, a consecutive cohort of 70 patients diagnosed with L5/S1 lumbar disc herniation (LDH) undergoing modified projection PEID was enrolled. Based on preoperative MRI (magnetic resonance imaging) evaluation of herniation types, they were divided into a central herniation group (n = 32) and a non-central herniation group (n = 38). Clinical outcomes and radiographic parameters were subsequently compared between the groups. Results: Seventy patients were included (38 non-central and 32 central). Baseline characteristics were comparable between the two groups except for a higher prevalence of bilateral symptoms in the central herniation group (p = 0.036). The central herniation group exhibited significantly shorter operative time (p = 0.027), reduced intraoperative blood loss (p = 0.047), and lower haemoglobin drop (p = 0.033). Multivariable linear regression confirmed that central herniation was independently associated with improved surgical efficiency. Both groups demonstrated significant postoperative improvements in VAS (Visual Analogue Scale) and JOA (Japanese Orthopaedic Association) scores. Although the non-central herniation group showed a higher JOA score on postoperative day 1 (p = 0.047), no significant differences were observed at 3 months or the final follow-up. The modified MacNab satisfaction rates were comparable (p = 0.411), with a similarly low complication rate in both groups. Conclusions: The modified PEID trajectory via the inferolateral margin of the L5 pedicle projection is feasible for central L5/S1 disc herniation and is associated with reduced operative time and decreased intraoperative blood loss. Full article
(This article belongs to the Special Issue Spine Surgery Innovations: Treatments and Technologies)
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13 pages, 687 KB  
Article
Recovery of Olfactory Function After Mepolizumab Treatment in Patients with Chronic Rhinosinusitis with Nasal Polyps: Influence of the Number of Surgeries
by Alda Cardesín, Ana Sogo, Aina Sansa, Mariana Campos, Carlota Rovira and Christian Domingo
Biomedicines 2026, 14(7), 1497; https://doi.org/10.3390/biomedicines14071497 - 2 Jul 2026
Viewed by 625
Abstract
Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease associated with significant olfactory dysfunction. The real-life effect of mepolizumab on smell recovery and the influence of prior surgery and peripheral eosinophilia remain unclear. Objective: Our objective [...] Read more.
Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease associated with significant olfactory dysfunction. The real-life effect of mepolizumab on smell recovery and the influence of prior surgery and peripheral eosinophilia remain unclear. Objective: Our objective was to evaluate olfactory outcomes after 12 months of mepolizumab in CRSwNP and analyze the impact of previous surgeries and baseline blood eosinophilia. Methods: This was a prospective observational study including 33 consecutive CRSwNP patients treated with mepolizumab. Olfactory function was assessed using subjective measures (VAS: Visual Analogue Scale; SNOT-22: Sino-nasal outcome test, item 21) and psychophysical testing (BOT-8: Barcelona Olfactory Test, detection and identification). Nasal Polyp Score (NPS), peripheral eosinophilia, and quality of life were recorded. Patients were stratified by number of prior sinonasal surgeries. Results: Significant improvement occurred in all subjective and objective olfactory measures at 12 months (BOT-8 detection: 100% vs. 0%; identification: 71% vs. 0%; VAS: 3 vs. 10; SNOT-22 item 21: 1 vs. 5; all p < 0.05). A lower improvement occurred in patients with ≥3 prior; however, this subgroup was small (p < 0.001). Baseline blood eosinophilia was not associated with olfactory improvement. Larger baseline polyp size correlated inversely with subjective olfactory gain (r = −0.48; p = 0.03). Conclusions: Twelve months of mepolizumab improved olfactory function in CRSwNP, especially in patients with fewer prior surgeries. Olfactory dysfunction responds to multifactorial mechanisms beyond blood eosinophilia, including tissue remodeling, nostril obstruction and possible neuroinflammatory mechanisms involving central olfactory pathways, supporting psychophysical test assessment and reinforcing olfaction as a marker of therapeutic response. Full article
(This article belongs to the Special Issue Biologic Drugs: The Evolution of Asthma Therapeutics)
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19 pages, 3047 KB  
Article
Spinal Versus General Anesthesia for Acute Kidney Injury and Transfusion in One-Week-Staged Bilateral Total Knee Arthroplasty
by Jaemin Lee, Jun Suh Moon and Doo Sup Kim
J. Clin. Med. 2026, 15(13), 4937; https://doi.org/10.3390/jcm15134937 - 25 Jun 2026
Viewed by 309
Abstract
Background/Objectives: Evidence on spinal versus general anesthesia in unilateral total knee arthroplasty (TKA) may not extend to one-week-staged bilateral surgery, where older patients receive two anesthetics in a short interval and intra-operative spinal-to-general conversion is common but rarely reported transparently. We compared peri-operative [...] Read more.
Background/Objectives: Evidence on spinal versus general anesthesia in unilateral total knee arthroplasty (TKA) may not extend to one-week-staged bilateral surgery, where older patients receive two anesthetics in a short interval and intra-operative spinal-to-general conversion is common but rarely reported transparently. We compared peri-operative acute kidney injury (AKI) and transfusion between strategies in this setting. Methods: We retrospectively analyzed 207 patients (414 surgeries) undergoing one-week-staged bilateral primary TKA at one center. Co-primary endpoints were creatinine-based AKI (patient level) and packed-red-blood-cell transfusion (surgery level). Because 42 general-anesthesia-classified surgeries had an attempted spinal injection, the primary analysis used the initial anesthetic plan (an intention-to-treat analogue), reclassifying these as spinal, with as-treated classification as a sensitivity analysis; AKI was modeled at the patient level (any general anesthesia versus spinal–spinal) and transfusion per surgery. Results: Median age was 75 years and 82.6% were female; AKI affected 74 of 207 patients (35.7%) and transfusion 185 of 414 surgeries (44.7%). The adjusted any-general-anesthesia versus spinal–spinal estimate was not statistically significant and opposite the spinal-protective hypothesis (adjusted odds ratio 0.49, 95% confidence interval 0.23–1.01, p = 0.054), and no pre-specified sensitivity scenario survived Benjamini–Hochberg correction. Transfusion did not differ between strategies; among secondary endpoints, length of stay, hemoglobin drop, peak C-reactive protein, and intra-operative hypotension likewise showed no significant difference after multiplicity correction. Conclusions: These hypothesis-generating findings do not support changing anesthetic practice; the choice should remain individualized. Approximately 12% of attempted spinal anesthetics converted intra-operatively to general anesthesia—a record-based observation, not a validated failure rate. Full article
(This article belongs to the Special Issue Clinical Management of Knee Arthroplasty)
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11 pages, 5809 KB  
Article
Effect of Biological Treatment in Uncontrolled Severe Chronic Rhinosinusitis with Polyps—A Real-Life Experience
by Na Sun, Ziye Huang and Yu Zhan
Biomedicines 2026, 14(6), 1228; https://doi.org/10.3390/biomedicines14061228 - 29 May 2026
Viewed by 427
Abstract
Background: The aim of this study was to evaluate the efficacy of mepolizumab as add-on therapy to intranasal corticosteroids (INCSs) for the treatment of severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNPs) in a real-life setting. Methods: This prospective observational study [...] Read more.
Background: The aim of this study was to evaluate the efficacy of mepolizumab as add-on therapy to intranasal corticosteroids (INCSs) for the treatment of severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNPs) in a real-life setting. Methods: This prospective observational study included 60 patients with severe uncontrolled CRSwNP who received mepolizumab. Follow-up assessments were performed at baseline (T0), 3 months (T1), and 6 months (T2). At each time point, patients underwent nasal endoscopy, completed the sinonasal outcome test-22 (SNOT-22), visual analogue scales (VAS) for smell, nasal obstruction and rhinorrhoea and facial pain. Nasal secretion and blood eosinophil counts (BECs) were also evaluated. The levels of eosinophil cationic protein (ECP) in nasal secretions were measured using an enzyme-linked immunosorbent assay (ELISA). Results: Both patient- and physician-derived outcome measures showed significant improvements from baseline to 3 months, and the benefits were maintained at 6 months. No major adverse events were reported. Conclusions: Mepolizumab was associated with improvements in nasal obstruction and sense of smell, based on both patient- and physician-derived outcome measures. However, due to the single-arm design and modest sample size, these findings should be considered hypothesis-generating rather than confirmatory. Full article
(This article belongs to the Special Issue Allergic Rhinitis: From Pathology to Novel Therapeutic Approaches)
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32 pages, 24154 KB  
Article
Structural Optimization of Pterostilbene, a Promising Lead Molecule, and Evaluation of Its Derivatives via ADMET Prediction and In Vitro/In Vivo Anti-Cerebral Ischemic Activity
by Kecan Zhang, Jiaxin Li, Yanan Dai and Zhihong Yang
Int. J. Mol. Sci. 2026, 27(10), 4512; https://doi.org/10.3390/ijms27104512 - 18 May 2026
Viewed by 513
Abstract
Pterostilbene (Pts), a small molecule stilbenoid and a dimethyl analogue of the star molecule resveratrol, exerts significant blood–brain barrier protection on cerebral ischemia-reperfusion injury and has received extensive attention. This study performed structural optimizations on Pts to obtain a series of derivatives and [...] Read more.
Pterostilbene (Pts), a small molecule stilbenoid and a dimethyl analogue of the star molecule resveratrol, exerts significant blood–brain barrier protection on cerebral ischemia-reperfusion injury and has received extensive attention. This study performed structural optimizations on Pts to obtain a series of derivatives and investigated their anti-ischemic activities both in vitro and in vivo, aiming to identify candidates with high safety and improved efficacy compared with Pts. The ADMET method was used to predict the drug-likeness of a series of Pts derivatives, and in vitro MTT cell viability analysis was conducted on neuroblastoma cells (SH-SY5Y) and brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation/reperfusion (OGD/R) injury. On the basis of the cytotoxicity results, four derivatives (NO. 1, NO. 3, NO. 5, and NO. 7) were selected for subsequent in vitro and in vivo biological activities evaluation. These compounds exhibited significantly higher TI values (18.29–30.61) in OGD/R-injured hBMECs compared with Pts (7.63) and effectively suppressed apoptosis, promoted cell migration, and enhanced tube formation capacity. In vivo, NO. 3 (5 mg/kg, ip., 7 d) demonstrated superior efficacy compared to Pts in improving cerebral blood flow, reducing infarction volume, enhancing neurological function, and modulating serum biomarker levels in middle cerebral artery occlusion/reperfusion (MCAO/R) rats, whereas NO. 1 and NO. 7 showed comparable efficacy to Pts. The acute intraperitoneal toxicity of NO. 3 was conducted and showed that the LD50 of NO. 3 was estimated to be more than 300 mg/kg. In this study, the rational design and comprehensive evaluation of Pts derivatives were reported. Compound NO. 3 demonstrated superior pharmacological efficacy to Pts both in vitro and in vivo, and it may be a promising therapeutic candidate for ischemic stroke intervention. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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13 pages, 5758 KB  
Communication
Short Communication: The Peripheral Cannabinoid CB1 Receptor Antagonist AM6545 Modifies Cardiovascular Effects of Endocannabinoids in DOCA-Salt Rats
by Patryk Remiszewski, Eberhard Schlicker, Emilia Grzęda, Jolanta Weresa, Marek Toczek and Barbara Malinowska
Int. J. Mol. Sci. 2026, 27(10), 4449; https://doi.org/10.3390/ijms27104449 - 15 May 2026
Viewed by 399
Abstract
Peripherally restricted (‘second-generation’) cannabinoid CB1 receptor (CB1R) antagonists have been suggested to have therapeutic potential in numerous diseases. However, their effects on the cardiovascular system require further research. The peripheral CB1R antagonist AM6545 failed to modify the decrease [...] Read more.
Peripherally restricted (‘second-generation’) cannabinoid CB1 receptor (CB1R) antagonists have been suggested to have therapeutic potential in numerous diseases. However, their effects on the cardiovascular system require further research. The peripheral CB1R antagonist AM6545 failed to modify the decrease in blood pressure (BP) elicited by inhibition of anandamide degradation in spontaneously hypertensive rats. The aims of the present study were to examine the effect of AM6545 on BP and its interaction with endocannabinoid-evoked effects in deoxycorticosterone acetate (DOCA)-salt rats. For this purpose, we applied methanandamide (MethAEA), a stable analogue of anandamide, and URB597, an inhibitor of its degradation, in urethane-anesthetized animals. AM6545 did not affect BP by itself. MethAEA elicited a biphasic effect (a rise in BP, followed by its fall); both phases were antagonized by AM6545. URB597 induced a monophasic hypotensive effect, which was abolished by AM6545 in DOCA-salt rats but further enhanced in control animals. AM6545 also unmasked an additional increase in BP after URB597 in both groups of rats. In conclusion, AM6545 modifies the cardiovascular effects of endocannabinoids in hypertension in a model-dependent manner. The cardiovascular effects of CB1R antagonists should be carefully evaluated when assessing their potential therapeutic significance, as they may unmask an increase in BP. Full article
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23 pages, 36098 KB  
Article
Nano-Enabled Potentiation of a Lead Mono-Carbonyl Curcumin Analogue via PEGylated Graphene Oxide for Enhanced Glycemic Control
by Babar Ayub, Haya Hussain, Farman Ali Khan, Nasir Mehmood Khan, Abid Ullah, Kifayat Ullah, Syed Wadood Ali Shah, Jian Wang and Shujaat Ahmad
Pharmaceutics 2026, 18(5), 568; https://doi.org/10.3390/pharmaceutics18050568 - 2 May 2026
Viewed by 1644
Abstract
Background: The global healthcare system faces a significant challenge due to the escalating prevalence of type 2 diabetes, affecting over 10% of the world’s population. Suppression of postprandial hyperglycemia through inhibition of carbohydrate-hydrolyzing enzymes is an effective therapeutic strategy. Although curcumin effectively inhibits [...] Read more.
Background: The global healthcare system faces a significant challenge due to the escalating prevalence of type 2 diabetes, affecting over 10% of the world’s population. Suppression of postprandial hyperglycemia through inhibition of carbohydrate-hydrolyzing enzymes is an effective therapeutic strategy. Although curcumin effectively inhibits α-amylase and α-glucosidase activities, its lower solubility and bioavailability restrict its clinical application. In this study, five mono-carbonyl curcumin analogues (CA1–CA5) were synthesized and evaluated for their antidiabetic potential following selective experimental methods both in vitro, and in vivo. Enhanced delivery for the most potent analogue was achieved through PEGylated graphene oxide (PEG-GO) to overcome the shortcomings of curcumin compounds. Methods: In silico ADME profiling was conducted using SwissADME, and molecular docking studies were performed with AutoDock Vina (v1.5.7) to assess enzyme binding interaction. The synthesized compounds were further evaluated using in vitro α-amylase and α-glucosidase inhibition assays, followed by in vivo blood profile analysis. The most active analogue CA3 (chloro derivative) was loaded onto PEG-GO and characterized using UV–visible spectroscopy, Fourier-transform infrared spectroscopy, and scanning electron microscopy. Results: Among all of the compounds, CA3 exhibits the strongest binding affinity and highest enzyme inhibitory activity, followed by CA2 and CA4. PEG-GO-CA3 demonstrated significantly enhanced biological activity compared to its free form. In vivo studies showed marked improvements in body weight and lipid profile, along with significant reductions in blood glucose, glycated hemoglobin, urea, creatinine, alanine aminotransferase, and aspartate aminotransferase levels over a 28-day treatment period as compared to a diabetic control. Spectroscopic and morphological analyses confirmed successful loading of CA3 onto PEG-GO (27.7–31.5%) with a release profile of 38–57% after 12 and 36 h in a controlled environment at pH 7. Conclusions: These findings suggest that PEG-GO-loaded mono-carbonyl curcumin analogues represent promising therapeutic candidates for the management of T2DM. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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38 pages, 3263 KB  
Article
Thiazolyl-Methylthio-1,3,4-Thiadiazole Hybrids as Halicin Analogues with Antimicrobial and Antibiofilm Activities: Chemical Development, Biological Assessment, and 2D-QSAR Study
by Daniel Ungureanu, Gabriel Marc, Mihaela Niculina Duma, Dan Cristian Vodnar, Gheorghe-Adrian Martău, Laurian Vlase, Adrian Pîrnău, Brîndușa Tiperciuc, Cristina Moldovan, Ioana Ionuț, Anca Stana, Ilioara Oniga and Ovidiu Oniga
Antibiotics 2026, 15(5), 448; https://doi.org/10.3390/antibiotics15050448 - 29 Apr 2026
Cited by 1 | Viewed by 772
Abstract
Background/Objectives: The purpose of this study was the chemical design, synthesis, and evaluation of the antimicrobial and antibiofilm potentials of 20 novel thiazolyl-methylthio-thiadiazole hybrid compounds (6aj and 8aj). Methods: The compounds were designed as structural [...] Read more.
Background/Objectives: The purpose of this study was the chemical design, synthesis, and evaluation of the antimicrobial and antibiofilm potentials of 20 novel thiazolyl-methylthio-thiadiazole hybrid compounds (6aj and 8aj). Methods: The compounds were designed as structural analogues of halicin with two points of variation and were synthesized through a process with multiple condensation steps. The compounds were evaluated in vitro through MIC determinations for the antimicrobial activity and percentage of biofilm inhibition, and in silico, respectively, through molecular docking, druggability, and ADMETox prediction. A 2D-QSAR study was conducted for antimicrobial activity using the Free-Wilson model. Results: In terms of antibacterial activity, all compounds displayed important activity on the tested strains (MICs = 15.62–250 μg/mL), except against Staphylococcus aureus. Regarding the antifungal activity, the effect against Candida albicans was similar to fluconazole in most cases (MIC = 15.62 μg/mL). With respect to the antibiofilm activity, the most effective activity was registered against the Pseudomonas aeruginosa biofilm. The in vitro results for the antibacterial activity against Escherichia coli were correlated with the observations drawn in the molecular docking study on the ATPase domain of the GyrB subunit of E. coli. The in silico predictions of the molecular properties concluded that all compounds have good druggability properties, while the ADMETox predictions concluded that the compounds could have low gastrointestinal absorption and blood–brain barrier permeation capacity, but raised safety flags (e.g., hepatotoxicity and high acute oral toxicity). The 2D-QSAR study concluded that the thiazolyl-methylthio-thiadiazole scaffold had the highest contribution to antimicrobial activity in almost all cases. Conclusions: The two series of compounds highlight the impact of structural modulations of the scaffold and its substituents on the investigated biological activities. Full article
(This article belongs to the Special Issue Antibiotic Synthesis, 2nd Edition)
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24 pages, 672 KB  
Systematic Review
Bloodstain Pattern Analysis in Crime Scene Investigation: A Systematic Literature Review
by Muhammad Jefri Mohd Yusof, Tharshini Chandran, Muhammad Reza Amin Reza Adnan, Eddy Saputra Rohmatul Amin, Sarah Aliah Amir Sarifudin and Nurul Ain Abu Bakar
Forensic Sci. 2026, 6(2), 38; https://doi.org/10.3390/forensicsci6020038 - 20 Apr 2026
Cited by 1 | Viewed by 2440
Abstract
Background/Objectives: Bloodstain pattern analysis (BPA) is widely used in crime scene investigation (CSI), yet its practical application, evidential limits, and interpretive role are often discussed in fragmented or technique-focused terms. This systematic literature review examines how BPA is used in CSI, with [...] Read more.
Background/Objectives: Bloodstain pattern analysis (BPA) is widely used in crime scene investigation (CSI), yet its practical application, evidential limits, and interpretive role are often discussed in fragmented or technique-focused terms. This systematic literature review examines how BPA is used in CSI, with emphasis on its operational functions, interpretive scope, and scientific robustness. Methods: The review followed PRISMA 2020 guidelines. A comprehensive search was conducted in Scopus using predefined Boolean strings. After screening, eligibility assessment, and manual review, 18 peer-reviewed research articles published between 1996 and 2026 were included. Data were extracted systematically and analysed using thematic synthesis. Results: The findings show that BPA is applied in CSI as an integrated evidential pathway rather than as a single analytical procedure. Its uses include bloodstain detection and documentation, geometric reconstruction through trajectory and area-of-origin analysis, differentiation of mechanisms and sources to prevent misclassification, activity-level inference based on transfer and contact phenomena, and temporal reasoning related to trace formation. The review also highlights the role of validation infrastructures, including blood substitutes, animal analogues, and computational methods, which support training, experimentation, and reproducibility under ethical and practical constraints. Across the literature, reconstruction accuracy is shown to be sensitive to documentation quality, measurement assumptions, environmental conditions, and contextual limitations. Conclusions: Overall, BPA contributes to CSI by enabling structured, context-aware interpretation of blood evidence while remaining subject to measurement assumptions, contextual influences, and cognitive factors that may affect reconstruction outcomes. Its evidential value lies not only in reconstructing events, but also in supporting transparent, testable, and defensible forensic reasoning. Full article
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18 pages, 3615 KB  
Article
Using the Scaffold of FDA-Approved Drugs with Trypanocidal Activity to Identify New Anti-Trypanosoma cruzi Agents: An In Silico and In Vitro Approach
by Lenci K. Vázquez-Jiménez, Alonzo González-González, Timoteo Delgado-Maldonado, Rogelio Gómez-Escobedo, Guadalupe Avalos-Navarro, Adriana Moreno-Rodríguez, Alma D. Paz-González, Eyra Ortiz-Pérez, Benjamín Nogueda-Torres and Gildardo Rivera
Molecules 2026, 31(8), 1327; https://doi.org/10.3390/molecules31081327 - 17 Apr 2026
Cited by 1 | Viewed by 708
Abstract
Chagas disease affects millions of people worldwide, including those in Latin America. The only drugs available for its treatment are benznidazole and nifurtimox. However, these drugs present high toxicity and limited efficacy. Therefore, the search for new treatments continues. In this regard, computer-assisted [...] Read more.
Chagas disease affects millions of people worldwide, including those in Latin America. The only drugs available for its treatment are benznidazole and nifurtimox. However, these drugs present high toxicity and limited efficacy. Therefore, the search for new treatments continues. In this regard, computer-assisted drug design has been implemented in scientific research for drug repurposing, allowing for reduced costs and time. Therefore, the objective of this work was to search for analogs of FDA-approved drugs with activity against Trypanosoma cruzi through ligand-based virtual screening and their biological evaluation against blood trypomastigotes. The compound TD-095 (LC50 = 48.60 and 13.75 µM), a ketanserin analogue, TS-936 (LC50 = 71.55 and 37.54 µM), a terfenadine analogue, and TD-831 (LC50 = 75.94 and 26.17 µM), a sulfasalazine analogue, were considered as potential trans-sialidase inhibitors; TIM-967 (LC50 = 69.70 and 39.69 µM) and LK-284 (LC50 = 116.7 and 82.29 µM), two sulfonylurea analogues, were considered as potential triosephosphate isomerase inhibitors, showing better trypanocidal activity against NINOA and INC-5 strains, respectively, than the reference drugs. Molecular dynamics simulations predicted the stability of the compounds in complex with their respective proteins. Finally, the ADMET predictive analysis showed favorable properties for the compounds. These results support continued research into new agents against Trypanosoma cruzi, using structures of drugs already approved by the FDA. Full article
(This article belongs to the Special Issue Novel Antiparasitic Molecules for Neglected Tropical Diseases)
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15 pages, 717 KB  
Review
Bypass Treatments for Primary Coenzyme Q10 Deficiency: An Update
by David Mantle, Neve Cufflin and Iain P. Hargreaves
Int. J. Mol. Sci. 2026, 27(8), 3526; https://doi.org/10.3390/ijms27083526 - 15 Apr 2026
Viewed by 1789
Abstract
Primary coenzyme Q10 (CoQ10) deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In humans, at least 10 genes (PDSS1, PDSS2 to COQ10) are required for the biosynthesis of functional CoQ10, a mutation in any one of [...] Read more.
Primary coenzyme Q10 (CoQ10) deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In humans, at least 10 genes (PDSS1, PDSS2 to COQ10) are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status and present as primary CoQ10 deficiency. Furthermore, the genes NDUFA9 and HPDL, whilst not part of the PDSS1, PDSS2 to COQ10 gene sequence, have also been shown to have a crucial role in CoQ10 biosynthesis. A major problem in treating primary CoQ10 deficiencies is the poor bioavailability of supplemental CoQ10, both in terms of lack of absorption from the digestive tract and inability to cross the human blood–brain barrier. Bypass strategies aim to circumvent this problem by using more bioavailable precursor analogues that can enter the cell and be incorporated into the CoQ10 synthesis pathway downstream of the affected enzyme, examples being 4-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid or vanillic acid, which, in contrast to CoQ10, are small, water-soluble molecules. In this article, we have, therefore, reviewed potential bypass mechanisms for primary CoQ10 deficiencies, PDSS1, PDSS2 to COQ10, together with NDUFA9 and HPDL, using such precursors. Most of the published data relating to the bypass therapy of primary CoQ10 deficiency is derived from cell lines or animal models, and few human studies have so far been undertaken. In addition, further research is required to investigate the potential mechanisms by which bypass compounds such as 4-HB may access the human blood–brain barrier (BBB), for example, using in vitro co-culture BBB model systems incorporating CoQ10-deficient neurons. Overall, the objective of this article is, therefore, to systematically review the available data for each of the primary CoQ10 deficiencies, PDSS1, PDSS2 to COQ10 together with NDUFA9 and HPDL, in particular to identify the clinical potential of such studies. Full article
(This article belongs to the Special Issue Mitochondrial Function and Therapies)
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14 pages, 1874 KB  
Systematic Review
Effect of Tranexamic Acid on Post-Operative Pain and Alveolar Osteitis Following Dental Extraction—A Systematic Review and Meta-Analysis of RCTs
by Valentino Vellone, Giulia Romanelli, Ahmad Shoeb Hashmi, Daniela Adamo, Pedro Sampaio, Marco Della Monaca and Valentino Valentini
Appl. Sci. 2026, 16(7), 3402; https://doi.org/10.3390/app16073402 - 31 Mar 2026
Viewed by 1049
Abstract
Alveolar osteitis (AO) and postoperative pain are common complications after dental extractions. Excessive fibrinolysis leading to premature clot loss contributes to AO. Tranexamic acid (TXA), an antifibrinolytic agent, may stabilize post-extraction blood clots and reduce AO, although evidence from randomized controlled trials (RCTs) [...] Read more.
Alveolar osteitis (AO) and postoperative pain are common complications after dental extractions. Excessive fibrinolysis leading to premature clot loss contributes to AO. Tranexamic acid (TXA), an antifibrinolytic agent, may stabilize post-extraction blood clots and reduce AO, although evidence from randomized controlled trials (RCTs) remains inconsistent. This systematic review and meta-analysis evaluated the effectiveness of topical TXA in preventing AO and reducing postoperative pain following dental extractions. PubMed, Embase, Scopus, and CENTRAL were searched from inception to June 2025 using terms related to “dental extraction” and “tranexamic acid”. Only English-language human studies were included. Eligible studies were RCTs assessing topical TXA versus placebo, saline, or plain gauze, reporting AO and/or pain outcomes. Non-RCTs, in vitro or animal studies, and trials lacking relevant outcomes or controls were excluded. Two reviewers independently screened and selected studies. Following PRISMA guidelines, two reviewers extracted data and assessed risk of bias with the Cochrane RoB-2 tool. Pooled analyses used random-effects models, with risk ratios (RRs) for AO and standardized mean differences (SMDs) for pain. AO was defined as exposed bone, foul odor, or persistent pain after day 3. Pain was measured on the Visual Analogue Scale (VAS) on days 3 and 7. Five RCTs (378 patients) were included. TXA significantly reduced AO incidence compared with controls (RR = 0.49; 95% CI: 0.32–0.76; p = 0.001; I2 = 0%), indicating a ~50% risk reduction. Pain outcomes showed no significant differences on day 3 (SMD = −0.36; 95% CI: −0.95 to 0.24; p = 0.24; I2 = 84%) or day 7 (SMD = −0.43; 95% CI: −1.34 to 0.48; p = 0.36; I2 = 93%). Topical TXA significantly reduces the risk of AO after dental extraction, while its effect on postoperative pain remains inconsistent. Its safety, accessibility, and low cost support its use as a preventive adjunct in dental extractions. Further standardized, high-quality RCTs are needed to clarify its role in pain management. Full article
(This article belongs to the Section Applied Dentistry and Oral Sciences)
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