Deciphering lung granulomas in HIV & TB co-infection: unveiling macrophages aggregation with IL6R/STAT3 activation.

Tuberculosis (TB) remains a leading cause of mortality among individuals coinfected with HIV, characterized by progressive pulmonary inflammation. Despite TB's hallmark being focal granulomatous lung lesions, our understanding of the histopathological features and regulation of inflammation in HIV & TB coinfection remains incomplete. In this study, we aimed to elucidate these histopathological features through an immunohistochemistry analysis of HIV & TB co-infected and TB patients, revealing marked differences. Notably, HIV & TB granulomas exhibited aggregation of CD68 + macrophage (Mφ), while TB lesions predominantly featured aggregation of CD20+ B cells, highlighting distinct immune responses in coinfection. Spatial transcriptome profiling further elucidated CD68+ Mφ aggregation in HIV & TB, accompanied by activation of IL6 pathway, potentially exacerbating inflammation. Through multiplex immunostaining, we validated two granuloma types in HIV & TB versus three in TB, distinguished by cell architecture. Remarkably, in the two types of HIV & TB granulomas, CD68 + Mφ highly co-expressed IL6R/pSTAT3, contrasting TB granulomas' high IFNGRA/SOCS3 expression, indicating different signaling pathways at play. Thus, activation of IL6 pathway may intensify inflammation in HIV & TB-lungs, while SOCS3-enriched immune microenvironment suppresses IL6-induced over-inflammation in TB. These findings provide crucial insights into HIV & TB granuloma formation, shedding light on potential therapeutic targets, particularly for granulomatous pulmonary under HIV & TB co-infection. Our study emphasizes the importance of a comprehensive understanding of the immunopathogenesis of HIV & TB coinfection and suggests potential avenues for targeting IL6 signaling with SOCS3 activators or anti-IL6R agents to mitigate lung inflammation in HIV & TB coinfected individuals.

The accuracy of intraocular lens power calculation formulas based on artificial intelligence in highly myopic eyes: a systematic review and network meta-analysis.

Objective: To systematically compare and rank the accuracy of AI-based intraocular lens (IOL) power calculation formulas and traditional IOL formulas in highly myopic eyes. Methods: We screened PubMed, Web of Science, Embase, and Cochrane Library databases for studies published from inception to April 2023. The following outcome data were collected: mean absolute error (MAE), percentage of eyes with a refractive prediction error (PE) within ±0.25, ±0.50, and ±1.00 diopters (D), and median absolute error (MedAE). The network meta-analysis was conducted by R 4.3.0 and STATA 17.0. Results: Twelve studies involving 2,430 adult myopic eyes (with axial lengths >26.0 mm) that underwent uncomplicated cataract surgery with mono-focal IOL implantation were included. The network meta-analysis of 21 formulas showed that the top three AI-based formulas, as per the surface under the cumulative ranking curve (SUCRA) values, were XGBoost, Hill-RBF, and Kane. The three formulas had the lowest MedAE and were more accurate than traditional vergence formulas, such as SRK/T, Holladay 1, Holladay 2, Haigis, and Hoffer Q regarding MAE, percentage of eyes with PE within ±0.25, ±0.50, and ±1.00 D. Conclusions: The top AI-based formulas for calculating IOL power in highly myopic eyes were XGBoost, Hill-RBF, and Kane. They were significantly more accurate than traditional vergence formulas and ranked better than formulas with Wang-Koch AL modifications or newer generations of formulas such as Barrett and Olsen. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022335969.

Tannic Acid-Aminated Sugar Beet Pectin Nanoparticles as a Stabilizer of High-Internal-Phase Pickering Emulsions.

Pickering stabilizers with additional antioxidant, photostabilizing, and metal-chelating properties are suitable for structuring multifunctional Pickering emulsion systems. Tannic acid (TA) is a potential material which when adsorbed onto the interface may impart antioxidant, UV-light-shielding, and chelating properties to Pickering stabilizers. Herein, we report a type of TA polyelectrolyte nanoparticles (NPs) fabricated following a complexation between TA and aminated sugar beet pectin (SBP-NH2). This study is geared toward investigating the performance of TA/SBP-NH2 NPs in stabilizing Pickering emulsions and protecting ß-carotene from degradation. TA/SBP-NH2 NPs formed under optimum conditions had a mean diameter of 82 nm with a sphere-like shape. Because of their favorable surface wettability (91.2°), TA/SBP-NH2 NPs promoted formation of the low-, medium-, and high-internal-phase Pickering emulsions (HIPEs) in an oil volume fraction (φ)-dependent manner; the TA/SBP-NH2 NP-stabilized HIPE demonstrated viscoelastic properties increasing with the increasing concentration (c) of nanoparticles. Due to the excellent storage stability and UV light-absorbing capacity, the photostability of ß-carotene was significantly improved by a TA/SBP-NH2 NP-stabilized HIPE (φ = 0.75; c = 3 mg/mL). Altogether, this study highlights that TA/SBP-NH2 NPs have potential applications in structuring Pickering emulsions with improved protective effects on loaded lipophilic compounds.

Grape seed proanthocyanidin-loaded gel-like W/O/W emulsion stabilized by genipin-crosslinked alkaline soluble polysaccharides-whey protein isolate conjugates: Fabrication, stability, and in vitro digestion.

The present work aims to fabricate the genipin-crosslinked alkaline soluble polysaccharides-whey protein isolate conjugates (G-AWC) to stabilize W/O/W emulsions for encapsulation and delivery of grape seed proanthocyanidins (GSP). After crosslinking reaction, the molecular weight was increased and surface hydrophobicity was decreased. Then, the G-AWC and polyglycerol polyricinoleate (PGPR, a lipophilic emulsifier) were employed to prepare a GSP-loaded W/O/W emulsion with the addition of gelatin and sucrose in W1 phase via a two-step procedure. Creamed emulsion could be fabricated at W1/O volume fraction (Φ) of 10%-70% and further increased Φ to 75% or even up to 90% could obtain gel-like emulsion with notably elastic behaviors. In the W1/O/W2 emulsion with Φ of 80%, the encapsulation efficiency (EE) of GSP reached up to 95.86%, and decreased by ca. 10% after a week of storage. Moreover, the encapsulated GSP in the emulsion showed a remarkably higher bioaccessibility (40.72%) compared to free GSP (13.11%) in the simulated gastrointestinal digestion. These results indicated that G-AWC-stabilized W/O/W emulsions could be an effective carrier to encapsulate water-soluble bioactive compounds with enhanced stability and bioaccessibility.

Robust W/O/W Emulsion Stabilized by Genipin-Cross-Linked Sugar Beet Pectin-Bovine Serum Albumin Nanoparticles: Co-encapsulation of Betanin and Curcumin.

Betanin and curcumin hold promise as natural colorants and antioxidants for food purposes due to their anti-hypertensive, anti-inflammation, and anti-tumor effects. However, the thermal stability and bioavailability of betanin and curcumin still need improvement. Here, we fabricated sugar beet pectin-bovine serum albumin nanoparticles (SBNPs) with a mean particle size of 180 ± 5.2 nm through a genipin cross-linking strategy to stabilize a type of Pickering water-in-oil-in-water (W/O/W) emulsion and co-encapsulated betanin and curcumin. First, the W1/O emulsion was homogenized with gelatin (the gelling agent) in the water phase and polyglycerol polyricinoleate (a lipophilic surfactant) in the oil phase. Later, W1/O was homogenized with another water phase containing SBNPs. The microstructure of the emulsion was regulated by the particle concentration (c) and W1/O volume fraction (Φ), especially the gel-like high internal phase emulsions were formed at the Φ up to 70%. In this case, betanin was encapsulated in the internal water phase (encapsulation efficiency = 65.3%), whereas curcumin was in the medium-chain triglyceride (encapsulation efficiency = 84.1%). Meanwhile, the shelf stability of betanin and curcumin was improved. Furthermore, the stability of bioactive compounds was potentiated by an emulsion gel in simulated gastrointestinal digestion, resulting in higher bioaccessibility. The aforementioned results suggest that SBNP-stabilized Pickering W/O/W emulsions could be a potential alternative to co-encapsulate betanin and curcumin with enhancement of shelf stability and bioaccessibility.

Molecular hybridization of grape seed extract: Synthesis, structural characterization and anti-proliferative activity in vitro.

The grape seed extract (GSE) hybridized with medium-chain saturated fatty acids (decanoic acid) exhibited higher lipophilicity, antioxidant activity, and anti-proliferative activity than its parents. The chemical structures of individual hybridized GSE derivatives were identified as 3'-O-decanoyl catechin, 3'-O-decanoyl epicatechin, 3', 5'-2-O-decanoyl epigallocatechin, and 3', 4', 3″, 5″-4-O-decanoyl epicatechin gallate by HPLC-MS2 and 1H and 13C NMR. For growth inhibitory effect on HepG2 cells, hybridized GSE derivatives (EC50 = 44.38 µg/mL) were significantly (p < 0.01) stronger than natural GSE (EC50 = 60.83 µg/mL) due to increased lipophilicity. The effects of GSE derivatives on apoptosis and cell cycle in HepG2 cells were further evaluated by flow cytometry. The results showed that the percentage of apoptotic cells increased markedly in the presence of hybridized GSE derivatives. Moreover, hybridized GSE derivatives were capable of inducing cell cycle arrest in G1 phase. This research suggests that hybridized GSE derivatives are effective lipophilic antioxidants and show the potential as adjuvant therapy for cancer.

Insights into the Regulation Effects of Certain Phenolic Acids on 2,3-Dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one Formation in a Microaqueous Glucose-Proline System.

The control of 2,3-dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one (DDMP) formation in the Maillard reaction is important to improve the thermally treated food quality as a result of its intense bitterness and potential toxicity. In this work, phenolic acids, such as gallic, protocatechuic, caffeic, and ferulic acids, were applied to modulate DDMP formation in a microaqueous glucose-proline model. The formation of DDMP was inhibited at low concentrations (from 0.1 to 5.0 mM) while enhanced at 10.0 mM gallic, protocatechuic, and caffeic acids. Ferulic acid always inhibited DDMP formation as a result of the absence of catechol groups on its benzene ring. The result indicated that the control of DDMP formation depended upon the concentration and chemical structures of phenolic acids, such as the number of hydroxyl groups. Further studies indicated that the hydroxyl distribution of phenolic acids regulated the peroxide formation in the model reaction system and further changed the development of the oxidation reaction, which affected the degradation of glucose via caramel or Maillard reaction, Amadori rearrangement product oxidation, and 1-deoxyglucosone degradation to form the intermediates.