Background and Aim
Previous smaller meta‐analyses comparing the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF) ...versus entecavir (ETV) provided controversial results. This updated meta‐analysis aimed to reliably identify any difference in the HCC incidence between TDF‐treated or ETV‐treated CHB patients in general or in specific subgroups.
Methods
PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies with hazard ratios (HRs) for HCC between TDF‐treated and ETV‐treated CHB patients. Retrieved dates ranged from January 2009 to October 2021. HRs with or without adjustment were pooled with random‐effects model.
Results
Twenty‐four comparative studies involving 37 771 CHB patients treated with TDF and 72 094 treated with ETV were included. TDF was associated with lower risk of HCC compared with ETV, with pooled unadjusted HR of 0.76 (95% confidence interval CI: 0.67–0.86) (24 studies) and adjusted HR of 0.81 (95% CI: 0.72–0.91) (21 studies). In propensity score matching cohorts, the TDF superiority was confirmed for unadjusted HR 0.83 (95% CI: 0.71–0.97) (14 studies) and was close to significance for adjusted HR (0.78, 95% CI: 0.58–1.04) (8 studies). Subgroup analyses showed that TDF was associated with lower HCC risk than ETV treatment in CHB patients who were from Asia (adjusted HR: 0.76, 95% CI: 0.66–0.87; 15 studies) or nucleos(t)ide naïve (adjusted HR:0.74, 95% CI: 0.65–0.84; 18 studies).
Conclusion
Current evidence from a sizable population suggests that TDF is associated with significantly lower HCC risk compared with ETV treatment in patients who are from Asia and/or nucleos(t)ide naïve.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
LINKED CONTENT
This article is linked to Vilar‐Gomez et al and Vilar‐Gomez and Chalasani papers. To view these articles, visit https://doi.org/10.1111/apt.15331 and https://doi.org/10.1111/apt.15486.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
A series of Ir(
iii
)-naproxen (NPX) conjugates with the molecular formula Ir(C^N)
2
bpy(4-CH
2
ONPX-4′-CH
2
ONPX)(PF
6
) (
Ir-NPX-1-3
) were designed and synthesized, including C^N = ...2-phenylpyridine (ppy,
Ir-NPX-1
), 2-(2-thienyl)pyridine (thpy,
Ir-NPX-2
) and 2-(2,4-difluorophenyl)pyridine (dfppy,
Ir-NPX-3
). Cytotoxicity tests showed that
Ir-NPX-1-3
exhibited excellent antitumor activity, especially in A549R cells. The cellular uptake experiment showed that the complexes were mainly localized in mitochondria, and induced apoptosis in A549R cells by damaging the structure and function of mitochondria. The main manifestations are a decrease in the mitochondrial membrane potential (MMP), an increase in reactive oxygen species (ROS) levels, and cell cycle arrest. Furthermore,
Ir-NPX-1-3
could inhibit the migration and colony formation of cancer cells, demonstrating potential anti-metastatic ability. Finally, the anti-inflammatory and immunological applications of
Ir-NPX-1-3
were verified. The downregulation of cyclooxygenase-2 (COX-2) and programmed death-ligand 1 (PD-L1) expression levels and the release of immunogenic cell death (ICD) related signaling molecules such as damage-associated molecular patterns (DAMPs) (cell surface calreticulin (CRT), high mobility group box 1 (HMGB1), and adenosine triphosphate (ATP)) indicate that these Ir(
iii
) -NPX conjugates are novel ICD inducers with synergistic effects in multiple anti-tumor pathways.
Novel Ir(
iii
)-naproxen (NPX) conjugates exhibit synergistic biological activity through anti-inflammatory, anti-metastasis, induction of apoptosis and immunotherapy.
(
) is a ubiquitous clinical fungal pathogen. In recent years, combination therapy, a potential treatment method to overcome
resistance, has gained traction. In this study, we synthesized a series of ...cyclometalated iridium(III) complexes with the formula Ir(C-N)
(tpphz)(PF
) (C-N = 2-phenylpyridine (ppy, in
), 2-(2-thienyl)pyridine (thpy, in
), 2-(2,4-difluorophenyl) pyridine (dfppy, in
), tpphz = tetrapyrido3,2-a:2',3'-c:3'',2''-h:2''',3'''-jphenazine) and polypyridyl ruthenium(II) complexes with the formula Ru(N-N)
(tpphz)(PF
)
(N-N = 2,2'-bipyridine (bpy, in
), 1,10-phenanthroline (phen, in
), 4,7-diphenyl-1,10-phenanthroline (DIP, in
)), and investigated their antifungal activities against drug-resistant
and their combination with fluconazole (FLC). Of which, the combination of the lead iridium(III) complex
and FLC showed strong antifungal activity against drug-resistant
Mechanism studies have shown that they can inhibit the formation of hyphae and biofilm, damage mitochondrial function and accumulate intracellular ROS. Therefore, iridium(III) complexes combined with FLC can be used as a promising treatment to exert anti-drug-resistant
activity, in order to improve the treatment efficiency of fungal infection.
Hippophae rhamnoides L. (sea buckthorn), consumed as a food and health supplement worldwide, has rich nutritional and medicinal properties. Different parts of H. rhamnoides L. were used in ...traditional Chinese medicines for relieving cough, aiding digestion, invigorating blood circulation, and alleviating pain since ancient times. Phytochemical studies revealed a wide variety of phytonutrients, including nutritional components (proteins, minerals, vitamins, etc.) and functional components like flavonoids (1–99), lignans (100–143), volatile oils (144–207), tannins (208–230), terpenoids (231–260), steroids (261–270), organic acids (271–297), and alkaloids (298–305). The pharmacological studies revealed that some crude extracts or compounds of H. rhamnoides L. demonstrated various health benefits, such as anti-inflammatory, antioxidant, hepatoprotective, anticardiovascular disease, anticancer, hypoglycemic, hypolipidemic, neuroprotective, antibacterial activities, and their effective doses and experimental models were summarized and analyzed in this paper. The quality markers (Q-markers) of H. rhamnoides L. were predicted and analyzed based on protobotanical phylogeny, traditional medicinal properties, expanded efficacy, pharmacokinetics and metabolism, and component testability. The applications of H. rhamnoides L. in juice, wine, oil, ferment, and yogurt were also summarized and future prospects were examined in this review. However, the mechanism and structure–activity relationship of some active compounds are not clear, and quality control and potential toxicity are worth further study in the future.
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The morphology of donor‐acceptor heterojunction interface significantly affects the electron/hole processes in organic solar cells, including charge transfer (CT), exciton dissociation (ED), and ...charge recombination (CR). Here, to investigate interface molecular configuration effects, the donor‐acceptor complexes with face‐on, edge‐on, and end‐on configurations were constructed as model systems for the p‐SIDT(FBTTh2)2/C60 heterojunction. The geometries, electronic structures, and excitation properties of monomers and the complexes with three configurations were studied based on density functional theory (DFT) and time‐dependent DFT calculations with optimally tuned range separation parameters and solid polarization effects. In terms of Marcus theory, the rate constants of ED and CR processes were analyzed. The results show that most of the excited states for p‐SIDT(FBTTh2)2 exhibit an intramolecular CT character, and the similarity of the excitation characters (CT and local excitation) and energies among three complexes with different configurations indicate that the electronic structure and excitation properties are insensitive to the interfacial molecular configurations. However, the rates of ED and CR processes heavily depend on it. These results underline the importance of controlling molecular configuration and then the morphology at the heterojunction interface in organic solar cells.
Based on density functional theory (DFT) and time‐dependent DFT calculations with optimally tuned range separation parameters and solid polarization effects, the exciton dissociation and charge recombination rates of p‐SIDT(FBTTh2)2/C60 complexes calculated using Marcus theory show that they strongly depend on the molecular configurations in an organic heterojunction interface.
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The design and synthesis of a series of metal complexes formed by non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen (IBP) and iridium(III), with the molecular formula ...Ir(C^N)2bpy(4-CH2OIBP-4’-CH2OIBP)(PF6) (Ir-IBP-1, Ir-IBP-2) (C^N = 2-phenylpyridine (ppy, Ir-IBP-1), 2-(2-thienyl)pyridine (thpy, Ir-IBP-2)) was introduced in this article. Firstly, it was found that the anti-proliferative activity of these complexes was more effective than that of cisplatin. Further research showed that Ir-IBP-1 and Ir-IBP-2 can accumulate in intracellular mitochondria, thereby disrupting mitochondrial membrane potential (MMP), increasing intracellular reactive oxygen species (ROS), blocking the G2/M phase of the cell cycle, and inducing cell apoptosis. In terms of protein expression, the expression of COX-2, MMP-9, NLRP3 and Caspase-1 proteins can be downregulated, indicating their ability to anti-inflammatory and overcome immune evasion. Furthermore, Ir-IBP-1 and Ir-IBP-2 can induce immunogenic cell death (ICD) by triggering the release of cell surface calreticulin (CRT), high mobility group box 1 (HMGB1) and adenosine triphosphate (ATP). Overall, iridium(III)-IBP conjugates exhibit various anti-tumor mechanisms, including mitochondrial damage, cell cycle arrest, inflammatory suppression, and induction of ICD.
Two novel cyclometalated iridium(III) complexes were designed and prepared by coupling with the nonsteroidal anti-inflammatory drug ibuprofen. These complexes can induce apoptosis in HeLa cells through mutiple action mechanisms, including mitochondrial damage, G2/M phase arrest, inflammatory suppression, and immunogenic cell death (ICD) induction. Display omitted
•Two novel ibuprofen (IBP) modified iridium(III) complexes (Ir(III)-IBP conjugates) were designed and synthesized.•Cytotoxicity tests showed that Ir(III)-IBP conjugates exhibited excellent antitumor activity.•Ir(III)-IBP conjugates could induce apoptosis in HeLa cells.•The anti-inflammatory and immunogenic cell death (ICD) induction ability of Ir(III)-IBP conjugates were verified.
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•Phyllanthus emblica Linn is an important plant for both medicine and food.•Phytonutrients (1–239) were classified and summarized from Phyllanthus emblica Linn.•Efficacy, bioactivity, ...and application of Phyllanthus emblica Linn are summarized.•The quality markers of Phyllanthus emblica Linn are reviewed for the first time.
Phyllanthus emblica Linn is not only an edible fruit with high nutritional value, but also a medicinal plant with multiple bioactivities. It is widely used in clinical practice with functions of clearing heat, cooling blood, digesting food, strengthening stomach, promoting fluid production, and relieving cough. This review summarized a wide variety of phytonutrients, including nutritional components (mineral elements, amino acids, vitamins, polysaccharides, unsaturated free fatty acids) and functional components (phenolic acids (1–34), tannins (35–98), flavonoids (99–141), sterols (142–159), triterpenoids (160–175), lignans (176–183), alkaloids (184–197), alkanes (198–212), aromatic micromolecules (213–222), other compounds (223–239)). The isolated compounds and the various extracts of P. emblica Linn presented a diverse spectrum of biological activities such as anti-oxidant, anti-cancer, anti-inflammatory, anti-bacterial, hepatoprotective, hypoglycemic, anti-atherosclerosis, neuroprotective, enhancing immunity, anti-fatigue, anti-myocardial fibrosis. The quality markers of P. emblica Linn were predicted and analyzed based on traditional medicinal properties, traditional efficacy, plant genealogy and chemical component characteristics, biogenic pathway of chemical components, measurability of chemical components, transformation characteristics of polyphenolic components, homologous characteristics of medicine and food, compound compatibility environment, and clinical applications. This review also summarized and prospected applications of P. emblica Linn in beverages, preserved fruits, fermented foods, etc. However, the contents of mechanism, structure-activity relationship, quality control, toxicity, extraction, processing of P. emblica Linn are not clear, and are worth further studies in the future.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
de Boiss is a common Tibetan medicine used for both medicine and food, belonging to the family Apiaceae. This plant has the functions of dispelling wind, removing dampness, dispersing cold, and ...relieving pain. It has great development potential and application prospects in food development and medicinal value.
The related references on botany, traditional uses, phytochemistry, quantitative analysis, and pharmacology of
de Boiss had been retrieved from both online and offline databases, including PubMed, ScienceDirect, Web of Science, Elsevier, Willy, SpringLink, SciFinder, Google Scholar, Baidu Scholar, ACS publications, SciHub, Scopus, and CNKI.
de Boiss exerts nourishing, appetizing, and digestive effects according to the theory of Tibetan medicine. Phytochemical reports have revealed that
de Boiss contains flavonoids, coumarins, sterols, and organic acids. Meanwhile, the quantitative analysis of the chemical constituents of
de Boiss has been done by means of UPLC-Q-TOF-MS. It has also been found that
de Boiss possesses multiple pharmacological activities, including anti-fatigue, anti-oxidant, anti-aging, and non-toxic activities.
This paper has comprehensively summarized botany, traditional uses, phytochemistry, quantitative analysis, and pharmacology of
de Boiss. It will not only provide an important clue for further studying
de Boiss, but also offer an important theoretical basis and valuable reference for in-depth research and exploitation of this plant in the future.
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