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1.
J Investig Med ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234011

RESUMO

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. The ability to predict whether a carcinoma would exhibit invasive ability in patients with PTC is important and has clinical implications for the selection of therapeutic strategies. Although several studies have focused on the genetic characterization of invasive cancer cells, the factors critical to the origination of invasive cancer cells are still unclear. This study aimed to determine whether genomic mutations contribute to the acquisition of the tumor invasion phenotype and to investigate the genetic features of invasive cancer cells in patients with PTC. We performed customized 48-gene deep exon sequencing in samples obtained from 88 patients with PTC via fine needle aspiration; the results revealed that no genetic changes were specifically associated with the tumor aggressiveness phenotype. Our results indicate that genetic mutations do not cause indolent PTCs to become invasive.

2.
Curr Biol ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34302743

RESUMO

In their pioneering study on dopamine release, Romo and Schultz speculated "...that the amount of dopamine released by unmodulated spontaneous impulse activity exerts a tonic, permissive influence on neuronal processes more actively engaged in preparation of self-initiated movements...."1 Motivated by the suggestion of "spontaneous impulses," as well as by the "ramp up" of dopaminergic neuronal activity that occurs when rodents navigate to a reward,2-5 we asked two questions. First, are there spontaneous impulses of dopamine that are released in cortex? Using cell-based optical sensors of extrasynaptic dopamine, [DA]ex,6 we found that spontaneous dopamine impulses in cortex of naive mice occur at a rate of ∼0.01 per second. Next, can mice be trained to change the amplitude and/or timing of dopamine events triggered by internal brain dynamics, much as they can change the amplitude and timing of dopamine impulses based on an external cue?7-9 Using a reinforcement learning paradigm based solely on rewards that were gated by feedback from real-time measurements of [DA]ex, we found that mice can volitionally modulate their spontaneous [DA]ex. In particular, by only the second session of daily, hour-long training, mice increased the rate of impulses of [DA]ex, increased the amplitude of the impulses, and increased their tonic level of [DA]ex for a reward. Critically, mice learned to reliably elicit [DA]ex impulses prior to receiving a reward. These effects reversed when the reward was removed. We posit that spontaneous dopamine impulses may serve as a salient cognitive event in behavioral planning.

3.
Nat Commun ; 12(1): 4409, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285209

RESUMO

Appetitive locomotion is essential for animals to approach rewards, such as food and prey. The neuronal circuitry controlling appetitive locomotion is unclear. In a goal-directed behavior-predatory hunting, we show an excitatory brain circuit from the superior colliculus (SC) to the substantia nigra pars compacta (SNc) to enhance appetitive locomotion in mice. This tectonigral pathway transmits locomotion-speed signals to dopamine neurons and triggers dopamine release in the dorsal striatum. Synaptic inactivation of this pathway impairs appetitive locomotion but not defensive locomotion. Conversely, activation of this pathway increases the speed and frequency of approach during predatory hunting, an effect that depends on the activities of SNc dopamine neurons. Together, these data reveal that the SC regulates locomotion-speed signals to SNc dopamine neurons to enhance appetitive locomotion in mice.


Assuntos
Comportamento Apetitivo/fisiologia , Locomoção/fisiologia , Parte Compacta da Substância Negra/fisiologia , Comportamento Predatório/fisiologia , Colículos Superiores/fisiologia , Animais , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Modelos Animais , Vias Neurais/fisiologia , Parte Compacta da Substância Negra/citologia , Técnicas Estereotáxicas , Colículos Superiores/citologia , Transmissão Sináptica/fisiologia
4.
J Transl Med ; 19(1): 291, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229717

RESUMO

Heart failure (HF) with preserved ejection fraction (HFpEF) is a leading cause of hospitalizations and mortality when diagnosed at the age of ≥ 65 years. HFpEF represents multifactorial and multisystemic syndrome and has different pathophysiology and phenotypes. Its diagnosis is difficult to be established based on left ventricular ejection fraction and may benefit from individually tailored approaches, underlying age-related changes and frequent comorbidities. Compared with the rapid development in the treatment of heart failure with reduced ejection fraction, HFpEF presents a great challenge and needs to be addressed considering the failure of HF drugs to improve its outcomes. Further extensive studies on the relationships between HFpEF, aging, and comorbidities in carefully phenotyped HFpEF subgroups may help understand the biology, diagnosis, and treatment of HFpEF. The current review summarized the diagnostic and therapeutic development of HFpEF based on the complex relationships between aging, comorbidities, and HFpEF.

5.
BMC Genomics ; 22(1): 495, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215185

RESUMO

BACKGROUND: The clearhead icefish, Protosalanx hyalocranius, is an economically important fishery species in China. Since 1980s, P. hyalocranius was widely introduced into lakes and reservoirs of northern China for aquaculture. However, the lack of a rapid and cost-effective sex identification method based on sex specific genetic markers has hindered study on sex determination mechanisms and breeding applications. RESULTS: Female-specific genomic regions were discovered by comparing whole genome re-sequencing data of both males and females. Two female-specific genomic regions larger than 50 bp were identified, and one (598 bp) contained a putative FOXI gene, which was paralogous to another FOXI gene with sex-associated SNPs. The two FOXI sequences displayed significant length difference with nine deletions of total length of 230 bp. This deletion-type structural variation could be easily and efficiently detected by traditional PCR and agarose gel electrophoresis with one 569 bp band for males and two bands (569 and 339 bp) for females, which were validated in 50 females and 40 males with known phenotypic sexes. CONCLUSIONS: The results provided structural genomic evidence for the ZZ/ZW sex determination system in P. hyalocranius discovered in our previous study with association analysis of SNPs. Moreover, the female-specific markers and rapid and cost-effective PCR-based genetic sex identification method should have applications in further studies of sex determination mechanism for this species.


Assuntos
Genoma , Osmeriformes , Animais , China , Feminino , Marcadores Genéticos , Genômica , Masculino , Osmeriformes/genética , Processos de Determinação Sexual
6.
Elife ; 102021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34269178

RESUMO

Vesicular neurotransmitter transporters (VNTs) mediate the selective uptake and enrichment of small molecule neurotransmitters into synaptic vesicles (SVs) and are therefore a major determinant of the synaptic output of specific neurons. To identify novel VNTs expressed on SVs (thus identifying new neurotransmitters and/or neuromodulators), we conducted localization profiling of 361 solute carrier (SLC) transporters tagging with a fluorescent protein in neurons, which revealed 40 possible candidates through comparison with a known SV marker. We parallelly performed proteomics analysis of immunoisolated SVs and identified 7 transporters in overlap. Ultrastructural analysis confirmed one of the transporters, SLC35D3, localized to SVs. Finally, by combining metabolite profiling with a radiolabeled substrate transport assay, we identified UDP-glucose as the principal substrate for SLC35D3. These results provide new insights into the functional role of SLC transporters in neurotransmission and improve our understanding of the molecular diversity of chemical transmitters.

7.
Nat Biotechnol ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294912

RESUMO

RNA N6-methyladenosine (m6A) modifications are essential in plants. Here, we show that transgenic expression of the human RNA demethylase FTO in rice caused a more than threefold increase in grain yield under greenhouse conditions. In field trials, transgenic expression of FTO in rice and potato caused ~50% increases in yield and biomass. We demonstrate that the presence of FTO stimulates root meristem cell proliferation and tiller bud formation and promotes photosynthetic efficiency and drought tolerance but has no effect on mature cell size, shoot meristem cell proliferation, root diameter, plant height or ploidy. FTO mediates substantial m6A demethylation (around 7% of demethylation in poly(A) RNA and around 35% decrease of m6A in non-ribosomal nuclear RNA) in plant RNA, inducing chromatin openness and transcriptional activation. Therefore, modulation of plant RNA m6A methylation is a promising strategy to dramatically improve plant growth and crop yield.

8.
Semin Liver Dis ; 41(3): 358-367, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34161994

RESUMO

Pruritus (itch) is a debilitating symptom in liver diseases with cholestasis, which severely affects patients' quality of life. Limited treatment options are available for cholestatic itch, largely due to the incomplete understanding of the underlying molecular mechanisms. Several factors have been proposed as pruritogens for cholestatic itch, such as bile acids, bilirubin, lysophosphatidic acid, and endogenous opioids. Recently, two research groups independently identified Mas-related G protein-coupled receptor X4 (MRGPRX4) as a receptor for bile acids and bilirubin and demonstrated its likely role in cholestatic itch. This discovery not only opens new avenues for understanding the molecular mechanisms in cholestatic itch but provides a promising target for developing novel anti-itch treatments. In this review, we summarize the current theories and knowledge of cholestatic itch, emphasizing MRGPRX4 as a bile acid and bilirubin receptor mediating cholestatic itch in humans. We also discuss some future perspectives in cholestatic itch research.

9.
Nat Commun ; 12(1): 3321, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059669

RESUMO

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder. The mechanisms underlying ASD are unclear. Astrocyte alterations are noted in ASD patients and animal models. However, whether astrocyte dysfunction is causal or consequential to ASD-like phenotypes in mice is unresolved. Type 2 inositol 1,4,5-trisphosphate 6 receptors (IP3R2)-mediated Ca2+ release from intracellular Ca2+ stores results in the activation of astrocytes. Mutations of the IP3R2 gene are associated with ASD. Here, we show that both IP3R2-null mutant mice and astrocyte-specific IP3R2 conditional knockout mice display ASD-like behaviors, such as atypical social interaction and repetitive behavior. Furthermore, we show that astrocyte-derived ATP modulates ASD-like behavior through the P2X2 receptors in the prefrontal cortex and possibly through GABAergic synaptic transmission. These findings identify astrocyte-derived ATP as a potential molecular player in the pathophysiology of ASD.


Assuntos
Trifosfato de Adenosina/metabolismo , Astrócitos/patologia , Transtorno do Espectro Autista/patologia , Sinalização do Cálcio/fisiologia , Receptores de Inositol 1,4,5-Trifosfato/deficiência , Animais , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/fisiopatologia , Comportamento Animal , Cálcio/metabolismo , Modelos Animais de Doenças , Neurônios GABAérgicos/fisiologia , Humanos , Receptores de Inositol 1,4,5-Trifosfato/genética , Masculino , Camundongos , Camundongos Knockout , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia , Transmissão Sináptica/fisiologia
10.
Neuron ; 109(13): 2165-2182.e10, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34048697

RESUMO

Drugs of abuse induce persistent remodeling of reward circuit function, a process thought to underlie the emergence of drug craving and relapse to drug use. However, how circuit-specific, drug-induced molecular and cellular plasticity can have distributed effects on the mesolimbic dopamine reward system to facilitate relapse to drug use is not fully elucidated. Here, we demonstrate that dopamine receptor D3 (DRD3)-dependent plasticity in the ventral pallidum (VP) drives potentiation of dopamine release in the nucleus accumbens during relapse to cocaine seeking after abstinence. We show that two distinct VP DRD3+ neuronal populations projecting to either the lateral habenula (LHb) or the ventral tegmental area (VTA) display different patterns of activity during drug seeking following abstinence from cocaine self-administration and that selective suppression of elevated activity or DRD3 signaling in the LHb-projecting population reduces drug seeking. Together, our results uncover how circuit-specific DRD3-mediated plasticity contributes to the process of drug relapse.


Assuntos
Prosencéfalo Basal/fisiologia , Cocaína/administração & dosagem , Dopamina/fisiologia , Comportamento de Procura de Droga/fisiologia , Habenula/fisiologia , Neurônios/fisiologia , Núcleo Accumbens/fisiologia , Receptores de Dopamina D3/fisiologia , Animais , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Recompensa , Área Tegmentar Ventral/fisiologia
11.
Genome ; : 1-14, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34058097

RESUMO

The basic leucine zipper (bZIP) family of genes encode transcription factors that play key roles in plant growth and development. In this study, a total of 92 HvbZIP genes were identified and compared with previous studies using recently released barley genome data. Two novel genes were characterized in this study, and some misannotated and duplicated genes from previous studies have been corrected. Phylogenetic analysis results showed that 92 HvbZIP genes were classified into 10 groups and three unknown groups. The gene structure and motif distribution of the three unknown groups implied that the genes of the three groups may be functionally different. Expression profiling indicated that the HvbZIP genes exhibited different patterns of spatial and temporal expression. Using qRT-PCR, more than 10 HvbZIP genes were identified with expression patterns similar to those of starch synthase genes in barley. Yeast one-hybrid analysis revealed that two of the HvbZIP genes exhibited in vitro binding activity to the promoter of HvAGP-S. The two HvbZIP genes may be candidate genes for further study to explore the mechanism by which they regulate the synthesis of barley starch.

12.
Environ Sci Pollut Res Int ; 28(24): 30459-30470, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33893912

RESUMO

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have gained increasing concern due to their persistent characteristics, wide distribution, biotoxicity, and bioaccumulative properties. The current remediation technologies for PFOA and PFOS are primarily focused on physical and chemical techniques. Phytoremediation has provided promising alternatives to traditional cleanup technologies due to their low operational costs, low maintenance requirements, end-use value, and aesthetic nature. In this review, uptake, translocation, and toxic effects of PFOS and PFOA are summarized and discussed. Several potential hyperaccumulators of PFOS and PFOA are provided according to the existing data. Biomass, chlorophyll, soluble protein, enzyme activities, oxidative stress, and other variables are assessed for potential indicator of PFOS/PFOA biotoxicity. The various studies on multiple scales are compared for identifying the threshold values. Several important implications and recommendations for future research are proposed at the end. This review provides an overview of current studies on plant uptake of PFOS and PFOA from the perspective of phytoremediation.


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Biodegradação Ambiental , Caprilatos
13.
Nat Neurosci ; 24(5): 746-752, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33821000

RESUMO

Serotonin (5-HT) is a phylogenetically conserved monoamine neurotransmitter modulating important processes in the brain. To directly visualize the release of 5-HT, we developed a genetically encoded G-protein-coupled receptor (GPCR)-activation-based 5-HT (GRAB5-HT) sensor with high sensitivity, high selectivity, subsecond kinetics and subcellular resolution. GRAB5-HT detects 5-HT release in multiple physiological and pathological conditions in both flies and mice and provides new insights into the dynamics and mechanisms of 5-HT signaling.


Assuntos
Neurônios/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Neurônios Serotoninérgicos/metabolismo , Serotonina/metabolismo , Animais , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Ratos , Transdução de Sinais/fisiologia
14.
Proc Natl Acad Sci U S A ; 118(15)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33833054

RESUMO

Learning and memory are assumed to be supported by mechanisms that involve cholinergic transmission and hippocampal theta. Using G protein-coupled receptor-activation-based acetylcholine sensor (GRABACh3.0) with a fiber-photometric fluorescence readout in mice, we found that cholinergic signaling in the hippocampus increased in parallel with theta/gamma power during walking and REM sleep, while ACh3.0 signal reached a minimum during hippocampal sharp-wave ripples (SPW-R). Unexpectedly, memory performance was impaired in a hippocampus-dependent spontaneous alternation task by selective optogenetic stimulation of medial septal cholinergic neurons when the stimulation was applied in the delay area but not in the central (choice) arm of the maze. Parallel with the decreased performance, optogenetic stimulation decreased the incidence of SPW-Rs. These findings suggest that septo-hippocampal interactions play a task-phase-dependent dual role in the maintenance of memory performance, including not only theta mechanisms but also SPW-Rs.

15.
Genome Biol ; 22(1): 111, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863366

RESUMO

BACKGROUND: Oncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference samples having a suitably large number of pre-identified variants for properly assessing oncopanel assay analytical quality and performance. The FDA-led Sequencing and Quality Control Phase 2 (SEQC2) consortium analyze ten diverse cancer cell lines individually and their pool, termed Sample A, to develop a reference sample with suitably large numbers of coding positions with known (variant) positives and negatives for properly evaluating oncopanel analytical performance. RESULTS: In reference Sample A, we identify more than 40,000 variants down to 1% allele frequency with more than 25,000 variants having less than 20% allele frequency with 1653 variants in COSMIC-related genes. This is 5-100× more than existing commercially available samples. We also identify an unprecedented number of negative positions in coding regions, allowing statistical rigor in assessing limit-of-detection, sensitivity, and precision. Over 300 loci are randomly selected and independently verified via droplet digital PCR with 100% concordance. Agilent normal reference Sample B can be admixed with Sample A to create new samples with a similar number of known variants at much lower allele frequency than what exists in Sample A natively, including known variants having allele frequency of 0.02%, a range suitable for assessing liquid biopsy panels. CONCLUSION: These new reference samples and their admixtures provide superior capability for performing oncopanel quality control, analytical accuracy, and validation for small to large oncopanels and liquid biopsy assays.

16.
Mamm Genome ; 32(3): 135-152, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33860357

RESUMO

DNA methylation is a stable and heritable epigenetic mechanism, of which the main functions are stabilizing the transcription of genes and promoting genetic conservation. In animals, the direct molecular inducers of DNA methylation mainly include histone covalent modification and non-coding RNA, whereas the fundamental regulators of DNA methylation are genetic and environmental factors. As is well known, competition is present everywhere in life systems, and will finally strike a balance that is optimal for the animal's survival and reproduction. The same goes for the regulation of DNA methylation. Genetic and environmental factors, respectively, are responsible for the programmed and plasticity changes of DNA methylation, and keen competition exists between genetically influenced procedural remodeling and environmentally influenced plastic alteration. In this process, genetic and environmental factors collaboratively decide the methylation patterns of corresponding loci. DNA methylation alterations induced by environmental factors can be transgenerationally inherited, and exhibit the characteristic of Lamarckian inheritance. Further research on regulatory mechanisms and the environmental plasticity of DNA methylation will provide strong support for understanding the biological function and evolutionary effects of DNA methylation.

17.
Basic Res Cardiol ; 116(1): 28, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33884509

RESUMO

Cardiac sympathetic overactivation is involved in arrhythmogenesis in patients with chronic heart failure (CHF). Inflammatory infiltration in the stellate ganglion (SG) is a critical factor for cardiac sympathoexcitation in patients with ventricular arrhythmias. This study aims to investigate if macrophage depletion in SGs decreases cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF. Surgical ligation of the coronary artery was used for induction of CHF. Clodronate liposomes were microinjected into bilateral SGs of CHF rats for macrophage depletion. Using cytokine array, immunofluorescence staining, and Western blot analysis, we found that macrophage expansion and expression of TNFα and IL-1ß in SGs were markedly increased in CHF rats. Flow cytometry data confirmed that the percentage of macrophages in SGs was higher in CHF rats than that in sham rats. Clodronate liposomes significantly reduced CHF-elevated proinflammatory cytokine levels and macrophage expansion in SGs. Clodronate liposomes also reduced CHF-increased N-type Ca2+ currents and excitability of cardiac sympathetic postganglionic neurons and inhibited CHF-enhanced cardiac sympathetic nerve activity. ECG data from 24-h, continuous telemetry recording in conscious rats demonstrated that clodronate liposomes not only restored CHF-induced heterogeneity of ventricular electrical activities, but also decreased the incidence and duration of ventricular tachycardia/fibrillation in CHF. Macrophage depletion with clodronate liposomes attenuated CHF-induced cardiac sympathetic overactivation and ventricular arrhythmias through reduction of macrophage expansion and neuroinflammation in SGs.

18.
Nat Commun ; 12(1): 1374, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654091

RESUMO

In many parts of the central nervous system, including the retina, it is unclear whether cholinergic transmission is mediated by rapid, point-to-point synaptic mechanisms, or slower, broad-scale 'non-synaptic' mechanisms. Here, we characterized the ultrastructural features of cholinergic connections between direction-selective starburst amacrine cells and downstream ganglion cells in an existing serial electron microscopy data set, as well as their functional properties using electrophysiology and two-photon acetylcholine (ACh) imaging. Correlative results demonstrate that a 'tripartite' structure facilitates a 'multi-directed' form of transmission, in which ACh released from a single vesicle rapidly (~1 ms) co-activates receptors expressed in multiple neurons located within ~1 µm of the release site. Cholinergic signals are direction-selective at a local, but not global scale, and facilitate the transfer of information from starburst to ganglion cell dendrites. These results suggest a distinct operational framework for cholinergic signaling that bears the hallmarks of synaptic and non-synaptic forms of transmission.


Assuntos
Acetilcolina/metabolismo , Sistema Nervoso Central/fisiologia , Transmissão Sináptica/fisiologia , Células Amácrinas/fisiologia , Células Amácrinas/ultraestrutura , Animais , Dendritos/fisiologia , Dendritos/ultraestrutura , Cinética , Camundongos Endogâmicos C57BL , Fótons , Células Ganglionares da Retina/ultraestrutura
19.
Bioorg Med Chem Lett ; 41: 127997, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33775839

RESUMO

Resistance phenomena during chemotherapy of tumor has been severely hampering the applications of chemotherapeutics. Due to advantage of drug repurposing, discovery of new chemosensitizers based on approved drugs is an effect strategy to find new candidates. Herein, we found antidepressant drug - sertraline, could sensitize drug-resistant gastric cancer cell (SGC-7901/DDP) with the IC50 value of 18.73 µM. To understand the structure-activity relationship and improve the activity, 30 derivatives were synthesized and evaluated. The IC50 value of the best compound was improved to 5.2 µM. Moreover, we found apoptosis induction and cell cycle arrest was the reason for the cell death of the drug-resistant cells after treatment of sertraline and derivatives, and PI3K/Akt/mTOR pathway was involved.

20.
IUBMB Life ; 73(5): 739-760, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33725395

RESUMO

Gastrointestinal symptoms and liver injury are common in patients with coronavirus disease 2019 (COVID-19). However, profiles of different pharmaceutical interventions used are relatively underexplored. Chinese herbal medicine (CHM) has been increasingly used for patients with COVID-19, but the efficacy of CHM used in COVID-19 on gastrointestinal symptoms and liver functions has not been well studied with definitive results based on the updated studies. The present study aimed at testing the efficacy of CHM on digestive symptoms and liver function (primary outcomes), the aggravation of COVID-19, and the time to viral assay conversion (secondary outcomes), among patients with COVID-19, compared with standard pharmacotherapy. The literature search was undertaken in 11 electronic databases from December 1, 2019 up to November 8, 2020. Appraisal of the evidence was conducted with Cochrane risk of bias tool or Newcastle Ottawa Scale. A random-effects model or subgroup analysis was conducted when significant heterogeneity was identified in the meta-analysis. The certainty of the evidence was assessed with the grading of recommendations assessment, development, and evaluation approach. Forty-eight included trials involving 4,704 participants were included. Meta-analyses favored CHM plus standard pharmacotherapy for COVID-19 on reducing the aggravation of COVID-19 and the time to viral assay conversion compared with standard pharmacotherapy. However, the present CHM as a complementary therapy for treating COVID-19 may not be beneficial for improving most gastrointestinal symptoms and liver function based on the current evidence. More well-conducted trials are warranted to confirm the potential efficacy of CHM furtherly.


Assuntos
COVID-19/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Adolescente , Adulto , Idoso , Anorexia/virologia , COVID-19/etiologia , Diarreia/tratamento farmacológico , Diarreia/virologia , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Gastroenteropatias/virologia , Humanos , Hepatopatias/etiologia , Hepatopatias/virologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Náusea/tratamento farmacológico , Náusea/virologia , Adulto Jovem
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