Prognostic Value of Non-HDL Cholesterol in COVID-19 Pneumonia. / Valor Prognóstico do Colesterol não HDL na Pneumonia por COVID-19.

BACKGROUND: In addition to coronary artery disease, non-high-density lipoprotein(non-HDL-C) provides short and long-term predictive information for many chronic inflammatory diseases such as stroke, hemodialysis, post-renal transplant, non-alcoholic hepatosteatosis, and human immunodeficiency virus. OBJECTIVES: This study examined the predictive value of non-HDL-C measured before SARS-CoV-2 for mortality in COVID-19 infection. METHODS: This study retrospectively included 1435 patients diagnosed with COVID-19 and treated in the thoracic diseases ward in a single center between January 2020 and June 2022. All patients included in the study had clinical and radiological features and signs of COVID-19 pneumonia. The COVID-19 diagnosis of all patients was confirmed by a polymerase chain reaction studied from an oropharyngeal swab. Statistical significance was set at p < 0.05. RESULTS: The study patients, including 1435 subjects, were divided into 712 patients in the non-surviving group and 723 in the surviving group. While there was no difference between the groups regarding gender, there was a statistically significant age difference. The non-surviving group was older. Age, lactate dehydrogenase(LDH), C reactive protein(CRP), triglycerides, D-dimer, and non-HDL-C were independent risk factors for mortality in regression analyses. In correlation analysis, age, CRP, and LDH were positively correlated with non-HDL-C. In the ROC analysis, sensitivity for non-HDL-C was 61.6%, and specificity was 89.2%. CONCLUSION: We believe that the non-HDL-C level studied before COVID-19 infection can be used as a prognostic biomarker for the disease.

FUNDAMENTO: Além da doença arterial coronariana, a lipoproteína de não alta densidade (não-HDL-C) fornece informações preditivas de curto e longo prazo para muitas doenças inflamatórias crônicas, como acidente vascular cerebral, hemodiálise, pós-transplante renal, hepatoesteatose não alcoólica e vírus da imunodeficiência humana. OBJETIVOS: Este estudo examinou o valor preditivo do não-HDL-C medido antes do SARS-CoV-2 para mortalidade na infecção por COVID-19. MÉTODOS: Este estudo incluiu retrospectivamente 1.435 pacientes diagnosticados com COVID-19 e tratados na enfermaria de doenças torácicas em um único centro entre janeiro de 2020 e junho de 2022. Todos os pacientes incluídos no estudo apresentavam características clínicas e radiológicas e sinais de pneumonia por COVID-19. O diagnóstico de COVID-19 de todos os pacientes foi confirmado por uma reação em cadeia da polimerase estudada a partir de um swab orofaríngeo. A significância estatística foi estabelecida em p < 0,05. RESULTADOS: Os pacientes do estudo, incluindo 1.435 indivíduos, foram divididos em 712 pacientes no grupo de não sobreviventes e 723 no grupo de sobreviventes. Embora não tenha havido diferença entre os grupos em relação ao sexo, houve uma diferença de idade estatisticamente significativa. O grupo que não sobreviveu era mais velho. Idade, lactato desidrogenase (LDH), proteína C reativa (PCR), triglicerídeos, D-dímero e não-HDL-C foram fatores de risco independentes para mortalidade em análises de regressão. Na análise de correlação, idade, PCR e LDH foram positivamente correlacionados com não-HDL-C. Na análise ROC, a sensibilidade para não-HDL-C foi de 61,6% e a especificidade foi de 89,2%. CONCLUSÃO: Acreditamos que o nível de não HDL-C estudado antes da infecção por COVID-19 pode ser usado como um biomarcador prognóstico para a doença.

The CH24H metabolite, 24HC, blocks viral entry by disrupting intracellular cholesterol homeostasis.

Cholesterol-24-hydroxylase (CH24H or Cyp46a1) is a reticulum-associated membrane protein that plays an irreplaceable role in cholesterol metabolism in the brain and has been well-studied in several neuro-associated diseases in recent years. In the present study, we found that CH24H expression can be induced by several neuroinvasive viruses, including vesicular stomatitis virus (VSV), rabies virus (RABV), Semliki Forest virus (SFV) and murine hepatitis virus (MHV). The CH24H metabolite, 24-hydroxycholesterol (24HC), also shows competence in inhibiting the replication of multiple viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 24HC can increase the cholesterol concentration in multivesicular body (MVB)/late endosome (LE) by disrupting the interaction between OSBP and VAPA, resulting in viral particles being trapped in MVB/LE, ultimately compromising VSV and RABV entry into host cells. These findings provide the first evidence that brain cholesterol oxidation products may play a critical role in viral infection.

High-Density Lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner.

There is a close relationship between the SARS-CoV-2 virus and lipoproteins, in particular high-density lipoprotein (HDL). The severity of the coronavirus disease 2019 (COVID-19) is inversely correlated with HDL plasma levels. It is known that the SARS-CoV-2 spike (S) protein binds the HDL particle, probably depleting it of lipids and altering HDL function. Based on neutron reflectometry (NR) and the ability of HDL to efflux cholesterol from macrophages, we confirm these observations and further identify the preference of the S protein for specific lipids and the consequent effects on HDL function on lipid exchange ability. Moreover, the effect of the S protein on HDL function differs depending on the individuals lipid serum profile. Contrasting trends were observed for individuals presenting low triglycerides/high cholesterol serum levels (LTHC) compared to high triglycerides/high cholesterol (HTHC) or low triglycerides/low cholesterol serum levels (LTLC). Collectively, these results suggest that the S protein interacts with the HDL particle and, depending on the lipid profile of the infected individual, it impairs its function during COVID-19 infection, causing an imbalance in lipid metabolism.

Optimizing lipid management-impact of the COVID 19 pandemic upon cardiovascular risk in England.

BACKGROUND: We sought to understand the impact of the COVID-19 pandemic on lipid-lowering therapy prescribing as a potential cause of the excess cardiovascular mortality seen post-pandemic in England. We examined temporal changes over 3 years in the prescribing of high-intensity and non-high-intensity statin therapy and ezetimibe. SOURCES OF DATA: We utilized data available via the National Health Service (NHS) Business Services Authority (NHSBSA) Information Services Data Warehouse, extracting 3 monthly data from October 2018 to December 2021 on high- and low-intensity statin and ezetimibe prescribing, (commencement, cessation or continuation) through each time period of study and those before, and after, the period of interest. AREAS OF AGREEMENT: Optimizing lipid management is a key component of the NHS Long Term Plan ambition to reduce deaths from cardiovascular disease, stroke and dementia. AREAS OF CONTROVERSY: The COVID-19 pandemic and associated lockdown have seen a significant reduction in prescribing of lipid-lowering therapies. If cardiovascular risk is not to worsen in the forthcoming years, urgent action is needed to ensure that the impact of the pandemic upon optimization of cholesterol and the historical undertreatment of cholesterol is reversed and improved. AREAS TIMELY FOR DEVELOPING RESEARCH: Prescription data available via NHSBSA can support our understanding of the implications of policy and behaviour and highlight the impact of guidelines in practise. GROWING POINTS: Understanding the impact of the COVID-19 pandemic upon cholesterol management and the opportunities for newer lipid-lowering therapies delivered using a population health approach have the potential to enhance lipid-lowering and improve cardiovascular mortality and morbidity and reduce health inequalities.

Laboratory Findings in Children with Excess Body Weight in Romania.

Background and Objectives: Childhood obesity has been increasing at a worrisome pace and emerging as a non-infectious pandemic in the pediatric population in recent years. Raising awareness on this problem is of utmost importance, in order to take action to control body weight from an early age. Materials and Methods: We performed a retrospective study among overweight or obese children evaluated on an outpatient basis in the Department of Pediatric Endocrinology of a tertiary care hospital in Bucharest Romania in 2021 in order to identify laboratory changes occurring according to age and sex. Results: A total of 268 children were included in the analysis, with a median age of 10.9 years (IQR: 8.3, 13.3 years); 61.8% were obese and 38.2% overweight. We identified a subclinical pro-inflammatory status characterized by increased neutrophil count (12.7%) and increased C-reactive protein (16.4%). Biochemically, we identified the highest increases for uric acid (35.4%). More than half of the children included in the study had dyslipidemia-specific changes: high low-density lipoprotein cholesterol (LDL) (50.0%), low high-density lipoprotein cholesterol (HDL) (58.9%) and increased triglyceride levels (12.7%), especially children with a body mass-index (BMI) percentile above 95%. Increased thyroid stimulating hormone (TSH) was identified in 20.3% and low thyroxine (T4) level in 13.4%, especially in females. Conclusions: Early measures to control excess body weight are needed since preventing obesity is easier than treating it. However, this is often difficult to do in our country because parents frequently do not recognize the problem until it is advanced. Furthermore, doctors are not always adequately prepared and sometimes they do not have the support of the health systems to provide children in need with the adequate care. Educational strategies and awareness of issue should be revisited in current post-pandemic context that facilitates increase of obesity prevalence in children. Increase of efficient communication could be achieved by pointing to these objective findings.

Effect of Cholesterol on Biomimetic Membrane Curvature and Coronavirus Fusion Peptide Encapsulation.

Biomimetic cubic phases can be used for protein encapsulation in a variety of applications such as biosensors and drug delivery. Cubic phases with a high concentration of cholesterol and phospholipids were obtained herein. It is shown that the cubic phase structure can be maintained with a higher concentration of biomimetic membrane additives than has been reported previously. Opposing effects on the curvature of the membrane were observed upon the addition of phospholipids and cholesterol. Furthermore, the coronavirus fusion peptide significantly increased the negative curvature of the biomimetic membrane with cholesterol. We show that the viral fusion peptide can undergo structural changes leading to the formation of hydrophobic α-helices that insert into the lipid bilayer. This is of high importance, as a fusion peptide that induces increased negative curvature as shown by the formation of inverse hexagonal phases allows for greater contact area between two membranes, which is required for viral fusion to occur. The cytotoxicity assay showed that the toxicity toward HeLa cells was dramatically decreased when the cholesterol or peptide level in the nanoparticles increased. This suggests that the addition of cholesterol can improve the biocompatibility of the cubic phase nanoparticles, making them safer for use in biomedical applications. As the results, this work improves the potential for the biomedical end-use applications of the nonlamellar lipid nanoparticles and shows the need of systematic formulation studies due to the complex interplay of all components.

Coronary microcirculatory dysfunction in hypercholesterolemic patients with COVID-19: potential benefit from cholesterol-lowering treatment.

Patients with hypercholesterolemia often have coronary microvascular dysfunction (CMD). Viral infections, such as the SARS-CoV-2 infection, may also result in CMD. Three non-randomized studies have shown significant beneficial effects of statins on CMD in non-infected patients. Similarly, in SARS-CoV-2 - infected patients one beneficial mechanism of action of statins may be the amelioration of endothelial dysfunction, which is a major driver of CMD. Apart from statins, lipoprotein apheresis and PCSK9 inhibitors can also improve or even reverse CMD. The potential reversal of CMD by using effective cholesterol-lowering medications during and after COVID-19 infection, especially in hypercholesterolemic COVID-19 patients, is important.KEY MESSAGESCoronary microvascular dysfunction (CMD) is common in patients hospitalized with SARS-CoV-2 infectionThree nonrandomized studies in non-infected patients are showing the beneficial effects of statin treatment on CMDEffective cholesterol-lowering medication during and after SARS-CoV-2 infection, especially in hypercholesterolemic COVID-19 patients, is of great significance.

Cholesterol-Amino-Phosphate (CAP) Derived Lipid Nanoparticles for Delivery of Self-Amplifying RNA and Restoration of Spermatogenesis in Infertile Mice.

Male infertility caused by genetic mutations is an important type of infertility. Currently, there is no reliable method in the clinic to address this medical need. The emergence of mRNA therapy provides a possible strategy for restoring mutant genes in the reproductive system. However, effective delivery of mRNA to spermatocytes remains a formidable challenge. Here a series of cholesterol-amino-phosphate (CAP) lipids are reported by integrating three bioactive moieties into a geometric structure, which is favorable for mRNA delivery. The results demonstrate that CAP-derived lipid nanoparticles (CAP LNPs) can deliver RNA including traditional mRNA and self-amplifying RNA (saRNA) encoding DNA Meiotic Recombinase 1 (Dmc1) protein in spermatocytes and treat male infertility caused by the Dmc1 gene mutation. Notably, the delivery efficiency of CAP LNPs is significantly higher than that of the MC3 and ALC-0315 LNPs, which is consistent with the design of CAP molecules. More importantly, a single injection of CAP LNPs-saRNA can produce Dmc1 protein for an extended period, which restores the spermatogenesis in the Dmc1 gene knockout mouse model. Overall, this study proves the concept of LNPs for the delivery of mRNA to spermatocytes, which provides a unique method to probe male infertility caused by the genetic mutation.

The Effect of Selected Flavonoids and Lipoic Acid on Natural and Model Cell Membranes: Langmuir and Microelectrophoretic Methods.

The influence of kaempferol (K), myricetin (M) and lipoic acid (LA) on the properties of natural erythrocytes, isolated from animal blood and biological membrane models (monolayers and liposomes) made of phosphatidylcholine (PC), cholesterol (CHOL), and sphingomyelin (SM), CHOL in a ratio of 10:9, was investigated. The Langmuir method, Brewster angle microscopy (BAM) and microelectrophoresis were used. The presented results showed that modification of liposomes with kaempferol, myricetin and lipoic acid caused changes in the surface charge density and the isoelectric point value. Comparing the tested systems, several conclusions were made. (1) The isoelectric point for the DPPC:Chol:M (~2.2) had lower pH values compared to lipoic acid (pH~2.5) and kaempferol (pH~2.6). (2) The isoelectric point for the SM-Chol with myricetin (~3.0) had lower pH values compared to kaempferol (pH~3.4) and lipoic acid (pH~4.7). (3) The surface charge density values for the DPPC:Chol:M system in the range of pH 2-9 showed values from 0.2 to -2.5 × 10-2 C m-2. Meanwhile, for the DPPC:Chol:K and DPPC:Chol:LA systems, these values were higher at pH~2 (0.7 × 10-2 C m-2 and 0.8 × 10-2 C m-2) and lower at pH~9 (-2.1 × 10-2 C m-2 and -1.8 × 10-2 C m-2), respectively. (4) The surface charge density values for the SM:Chol:M system in the range of pH 2-9 showed values from 0.5 to -2.3 × 10-2 C m-2. Meanwhile, for the DPPC:Chol:K and DPPC:Chol:LA systems, these values were higher at pH~2 (0.8 × 10-2 C m-2), and lower at pH~9 (-1.0 × 10-2 C m-2 and -1.8 × 10-2 C m-2), respectively. (5) The surface charge density values for the erythrocytes with myricetin in the range of pH 2-9 showed values from 1.0 to -1.8 × 10-2 C m-2. Meanwhile, for the erythrocytes:K and erythrocytes:LA systems, these values, at pH~2, were 1.3 × 10-2 C m-2 and 0.8 × 10-2 C m-2 and, at pH~9, -1.7 × 10-2 C m-2 and -1.0 × 10-2 C m-2, respectively.

Safety and Efficacy of Topical Lovastatin Plus Cholesterol Cream vs Topical Lovastatin Cream Alone for the Treatment of Disseminated Superficial Actinic Porokeratosis: A Randomized Clinical Trial.

Importance: Disseminated superficial actinic porokeratosis (DSAP) is an inherited or sporadic disorder of keratinization associated with germline variations. There is no effective standard of care therapy for DSAP, but treatment with topical lovastatin combined with cholesterol cream has shown promise. Objectives: To evaluate and compare the safety and efficacy of topical lovastatin 2% plus cholesterol 2% cream (lovastatin-cholesterol) and topical lovastatin 2% cream (lovastatin) alone in adults diagnosed with DSAP. Design, Setting, and Participants: This patient- and assessor-blinded, randomized clinical trial was conducted at the Medical University of South Carolina between August 3, 2020, and April 28, 2021. Nonpregnant adults with a previous clinical or histological diagnosis of DSAP were eligible. Data were blindly analyzed after study completion. Interventions: Participants were randomized to once- or twice-daily application of either lovastatin-cholesterol cream (n = 17) or lovastatin cream (n = 14) to symptomatic regions for 12 weeks. Main Outcomes and Measures: The primary efficacy measure was the effect of the treatment on DSAP at the end of treatment (12 weeks) as measured by the DSAP General Assessment Severity Index (DSAP-GASI; scored from 0-4, with 0 indicating clear and 4 indicating severe). Treatment efficacy was based on investigator-standardized photographs provided by the participants because of the need for evaluation via telehealth during the COVID-19 pandemic. Secondary efficacy measures included patient-reported outcomes, application frequency, and adverse events (AEs). Results: Of the 87 participants screened, 32 were enrolled. One participant randomized to receive lovastatin-cholesterol did not receive the intervention, leaving 17 participants (mean [range] age, 59.2 [40-83] years; 13 females [76.5%]; all White) allocated to receive lovastatin-cholesterol treatment and 14 participants (13 female [92.9%]; mean (range) age, 53.7 [33-71] years; all White) to receive lovastatin treatment. Twelve participants in each treatment group qualified for the analysis. Disease severity decreased from week 1 to week 12 by 50.0% (from 3.08 [95% CI, 2.57-3.60] to 1.54 (95% CI, 1.04-2.05] points on the DSAP-GASI; P < .001) in the lovastatin-cholesterol group and 51.4% (from 2.92 [95% CI, 2.40-3.43] to 1.50 [95% CI, 0.99-2.01] points; P < .001) in the lovastatin group. There was no significant difference between the treatment groups according to application frequency at the end of 12 weeks. Adverse events reported included myalgia (n = 2), elevation in the creatine kinase level (n = 1), application discomfort (n = 4), and rash (n = 1). No serious AEs occurred, and all participants with an AE were able to complete the study. Conclusions and Relevance: This randomized clinical trial found improvements in DSAP severity in both treatment groups, without serious AEs, indicating a limited benefit with the addition of cholesterol. These results suggest that lovastatin cream may be a new primary treatment option for patients diagnosed with DSAP. Trial Registration: ClinicalTrials.gov Identifier: NCT04359823.

Porcine Enteric Alphacoronavirus Entry through Multiple Pathways (Caveolae, Clathrin, and Macropinocytosis) Requires Rab GTPases for Endosomal Transport.

Porcine enteric alphacoronavirus (PEAV) is a new bat HKU2-like porcine coronavirus, and its endemic outbreak has caused severe economic losses to the pig industry. Its broad cellular tropism suggests a potential risk of cross-species transmission. A limited understanding of PEAV entry mechanisms may hinder a rapid response to potential outbreaks. This study analyzed PEAV entry events using chemical inhibitors, RNA interference, and dominant-negative mutants. PEAV entry into Vero cells depended on three endocytic pathways: caveolae, clathrin, and macropinocytosis. Endocytosis requires dynamin, cholesterol, and a low pH. Rab5, Rab7, and Rab9 GTPases (but not Rab11) regulate PEAV endocytosis. PEAV particles colocalize with EEA1, Rab5, Rab7, Rab9, and Lamp-1, suggesting that PEAV translocates into early endosomes after internalization, and Rab5, Rab7, and Rab9 regulate trafficking to lysosomes before viral genome release. PEAV enters porcine intestinal cells (IPI-2I) through the same endocytic pathway, suggesting that PEAV may enter various cells through multiple endocytic pathways. This study provides new insights into the PEAV life cycle. IMPORTANCE Emerging and reemerging coronaviruses cause severe human and animal epidemics worldwide. PEAV is the first bat-like coronavirus to cause infection in domestic animals. However, the PEAV entry mechanism into host cells remains unknown. This study demonstrates that PEAV enters into Vero or IPI-2I cells through caveola/clathrin-mediated endocytosis and macropinocytosis, which does not require a specific receptor. Subsequently, Rab5, Rab7, and Rab9 regulate PEAV trafficking from early endosomes to lysosomes, which is pH dependent. The results advance our understanding of the disease and help to develop potential new drug targets against PEAV.

Membrane cholesterol regulates the oligomerization and fusogenicity of SARS-CoV fusion peptide: implications in viral entry.

N-terminal residues (770-788) of the S2 glycoprotein of severe acute respiratory syndrome coronavirus (SARS-CoV) have been recognized as a potential fusion peptide that can be involved in the entry of the virus into the host cell. Membrane composition plays an important role in lipid-peptide interaction and the oligomeric status of the peptide. SARS-CoV fusion peptide (S2 fusion peptide) is known to undergo cholesterol-dependent oligomerization in the membrane; however, its significance in membrane fusion is still speculative. This study aimed to investigate the oligomerization of SARS-CoV fusion peptide in a membrane containing phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol, with varying concentrations of cholesterol, and to evaluate peptide-induced membrane fusion to correlate the importance of peptide oligomerization with membrane fusion. Peptide-induced modulation of membrane organization and dynamics was explored by steady-state and time-resolved fluorescence spectroscopic measurements using depth-dependent probes. The results clearly demonstrated the induction of S2 fusion peptide oligomerization by membrane cholesterol and the higher efficiency of the oligomer in promoting membrane fusion compared to its monomeric counterpart. Cholesterol-dependent peptide oligomerization and membrane fusion are important aspects of viral infection since the cholesterol level can change with age as well as with the onset of various pathophysiological conditions.

Overall and Sex-Specific Effect of Berberine for the Treatment of Dyslipidemia in Adults: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: Berberine is a nutraceutical that can improve lipid metabolism. Berberine may also affect sex hormones and exert sex-specific lipid-modifying effects, which have been overlooked. This study aimed to comprehensively review the efficacy and safety of berberine in adults for the treatment of dyslipidemia with consideration of potential sex disparity. Data Sources We searched Medline, Embase, Wanfang, CNKI, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform from inception to 13 December 2022. No language restrictions were applied. This study was registered in PROSPERO (CRD42021293218) prior to completing the literature search. Study Selection Two blinded reviewers assessed studies for inclusion. Eligible studies were randomized controlled trials in adults that compared berberine versus placebo, and measured blood lipids or lipoproteins. Data Extraction and Synthesis Data extraction was performed by two blinded reviewers using a structured form in Covidence. Risk of bias was assessed using the Cochrane risk of bias tool for randomized trials. Mean differences (MD) were estimated using inverse variance weighting with random effects models for lipid outcomes using R. Adverse events (AEs) were described narratively. Main Outcomes Primary outcomes were low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoprotein B. Secondary outcomes were gastrointestinal and muscle-related AEs. RESULTS: Eighteen studies (n = 1788 participants), conducted mainly in mainland China and Hong Kong (15 studies [83%]), were included with treatment durations ranging from 4 to 24 weeks. Berberine reduced LDL cholesterol (- 0.46 mmol/L, 95% CI - 0.62 to - 0.30, 14 studies, n = 1447), total cholesterol (- 0.48 mmol/L, 95% CI - 0.63 to - 0.33, 17 studies, n = 1637), triglycerides (- 0.34 mmol/L, 95% CI - 0.46 to - 0.23, 18 studies, n = 1661) and apolipoprotein B (- 0.25 g/L, 95% CI - 0.40 to - 0.11, 2 studies, n = 127). Berberine increased HDL cholesterol by 0.06 mmol/L (95% CI 0.00 to 0.11, 15 studies, n = 1471). Notably, the effect on HDL cholesterol was different in women (0.11 mmol/L, 95% CI 0.09 to 0.13) from that in men (- 0.07 mmol/L, 95% CI - 0.16 to 0.02). Among 16 studies that reported AEs, no serious AEs were reported for berberine. Gastrointestinal AEs were reported in 12 studies and tended to be more frequent in participants allocated to berberine versus placebo (2-23% vs 2-15%). CONCLUSIONS: Berberine produces small reductions in LDL cholesterol, triglycerides, and apolipoprotein B, with potential sex-specific effects on HDL cholesterol. Large-scale trials that consider sex disparity and assess clinical outcomes are required.

Berberine is found naturally in barberry and goldenthread, plants which have long been used in traditional herbal medicine in Asia. Nowadays berberine is used as a purified product and is easy to purchase as a nutraceutical supplement or non-prescription drug. People with dyslipidemia, a medical condition often known as 'high cholesterol', may prefer treatment with a nutraceutical such as berberine to reduce blood cholesterol. In recent years, many studies have contrasted the effects of taking berberine with an inactive placebo. This study aimed to combine all the available randomized controlled trials that assessed berberine's effects on blood lipids and lipoproteins. We included 18 studies that used berberine doses of 900­1500 mg/day, the majority of which were conducted in mainland China and Hong Kong. We found that on average berberine can modestly reduce low-density lipoprotein (LDL) cholesterol by 0.5 mmol/L (18 mg/dL) and triglycerides by 0.3 mmol/L (30 mg/dL). Berberine also increases high-density lipoprotein (HDL) cholesterol by 0.06 mmol/L (2 mg/dL). Interestingly, women may obtain a greater increase in HDL cholesterol than men. The short-term use of berberine appears to be safe. No study participants treated with berberine experienced a serious adverse event. However, berberine may occasionally cause constipation, diarrhea, or nausea. Larger high-quality studies are still needed to determine the long-term effects of berberine for dyslipidemia.

Plasma Apolipoprotein Concentrations Are Highly Altered in Severe Intensive Care Unit COVID-19 Patients: Preliminary Results from the LIPICOR Cohort Study.

SARS-CoV-2 infection goes beyond acute pneumonia, as it also impacts lipid metabolism. Decreased HDL-C and LDL-C levels have been reported in patients with COVID-19. The lipid profile is a less robust biochemical marker than apolipoproteins, components of lipoproteins. However, the association of apolipoprotein levels during COVID-19 is not well described and understood. The objective of our study is to measure plasma levels of 14 apolipoproteins in patients with COVID-19 and to evaluate the relationships between apolipoprotein levels, severity factors and patient outcomes. From November to March 2021, 44 patients were recruited on admission to the intensive care unit because of COVID-19. Fourteen apolipoproteins and LCAT were measured by LC-MS/MS in plasma of 44 COVID-19 patients on admission to the ICU and 44 healthy control subjects. Absolute apolipoprotein concentrations were compared between COVID-19 patients and controls. Plasma apolipoproteins (Apo) A (I, II, IV), C(I, II), D, H, J and M and LCAT were lower in COVID-19 patients, whereas Apo E was higher. COVID-19 severity factors such as PaO2/FiO2 ratio, SO-FA score and CRP were correlated with certain apolipoproteins. Lower Apo B100 and LCAT levels were observed in non-survivors of COVID-19 versus survivors. To conclude, in this study, lipid and apolipoprotein profiles are altered in COVID-19 patients. Low Apo B100 and LCAT levels may be predictive of non-survival in COVID-19 patients.

Potential use of the cholesterol transfer inhibitor U18666A as an antiviral drug for research on various viral infections.

Cholesterol plays critical functions in arranging the biophysical attributes of proteins and lipids in the plasma membrane. For various viruses, an association with cholesterol for virus entrance and/or morphogenesis has been demonstrated. Therefore, the lipid metabolic pathways and the combination of membranes could be targeted to selectively suppress the virus replication steps as a basis for antiviral treatment. U18666A is a cationic amphiphilic drug (CAD) that affects intracellular transport and cholesterol production. A robust tool for investigating lysosomal cholesterol transfer and Ebola virus infection is an androstenolone derived termed U18666A that suppresses three enzymes in the cholesterol biosynthesis mechanism. In addition, U18666A inhibited low-density lipoprotein (LDL)-induced downregulation of LDL receptor and triggered lysosomal aggregation of cholesterol. According to reports, U18666A inhibits the reproduction of baculoviruses, filoviruses, hepatitis, coronaviruses, pseudorabies, HIV, influenza, and flaviviruses, as well as chikungunya and flaviviruses. U18666A-treated viral infections may act as a novel in vitro model system to elucidate the cholesterol mechanism of several viral infections. In this article, we discuss the mechanism and function of U18666A as a potent tool for studying cholesterol mechanisms in various viral infections.

Predictors of COVID-19 severity among pregnant patients.

Coronavirus disease 2019 (COVID-19) was declared a pandemic and has spread around the globe, unsparingly affecting vulnerable populations. Effective prevention measures for pregnant women, who are particularly affected, include early identification of those patients at risk of developing in-hospital complications, and the continuous improvement of maternal-fetal treatment strategies to ensure the efficient use of health resources. The objective of our retrospective study was to determine which patient biomarkers on hospital admission correlate with disease severity as measured by disease course classification, the need for oxygen supplementation and higher demand for oxygen, the need for mechanical ventilation, intensive care unit admission, and length of hospital stay. Analysis of 52 PCR SARS-CoV-2 positive pregnant women revealed that the median date of hospital admission was the 30th gestational week, with dyspnoea, cough, and fever as the leading symptoms. The presence of diabetes and hypertension predisposed pregnant women to the severe course of illness. Lung involvement shown by CT scans on admission correlated with the greater clinical severity. The main laboratory predictors of disease progression were lymphocytopenia, hypocalcemia, low total cholesterol, low total protein levels, and high serum levels of C-reactive protein, ferritin, interleukin-6, glucose, lactate dehydrogenase, procalcitonin, and troponin I. Further research with a larger cohort of pregnant women is needed to determine the utility of these results for everyday practice.

Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk.

BACKGROUND: High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels. METHODS: In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.2-mg tablets twice daily) or matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy or could not receive statin therapy without adverse effects and had low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter or lower. The primary efficacy end point was a composite of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. RESULTS: Among 10,497 patients (66.9% with previous cardiovascular disease), the median baseline fasting triglyceride level was 271 mg per deciliter, HDL cholesterol level 33 mg per deciliter, and LDL cholesterol level 78 mg per deciliter. The median follow-up was 3.4 years. As compared with placebo, the effects of pemafibrate on lipid levels at 4 months were -26.2% for triglycerides, -25.8% for very-low-density lipoprotein (VLDL) cholesterol, -25.6% for remnant cholesterol (cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling), -27.6% for apolipoprotein C-III, and 4.8% for apolipoprotein B. A primary end-point event occurred in 572 patients in the pemafibrate group and in 560 of those in the placebo group (hazard ratio, 1.03; 95% confidence interval, 0.91 to 1.15), with no apparent effect modification in any prespecified subgroup. The overall incidence of serious adverse events did not differ significantly between the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a lower incidence of nonalcoholic fatty liver disease. CONCLUSIONS: Among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received pemafibrate than among those who received placebo, although pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels. (Funded by the Kowa Research Institute; PROMINENT ClinicalTrials.gov number, NCT03071692.).

Dyslipidemia and SARS-CoV-2 spike antibody titres after the second and third doses of the BNT162b2 vaccine among healthcare workers in Japan.

OBJECTIVE: This study aimed to examine the sex-associated differences in the relationship between dyslipidemia and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike immunoglobulin (Ig)G antibodies among BNT162b2 vaccine recipients. METHODS: Participants were staff members (aged 21-75 years) of a medical and research institution who underwent an anti-SARS-CoV-2 spike IgG antibody test after the second (n = 1872) and third doses (n = 1075) of the BNT162b2 vaccine. Dyslipidemia was defined as triglyceride level ≥150 mg/dl, high-density lipoprotein-cholesterol level <40 mg/dl, low-density lipoprotein-cholesterol level ≥140 mg/dl, or lipid-lowering medication use. Multivariable linear regression was used to calculate the ratio of means for SARS-CoV-2 spike IgG titre according to dyslipidemia status. RESULTS: The prevalence of dyslipidemia was 38.0% in men and 19.6% in women. The relationship between dyslipidemia and SARS-CoV-2 spike IgG titres after the second dose differed markedly by sex (P for interaction <0.001). In men, dyslipidemia was associated with significantly lower IgG titres: the ratio of means (95% confidence interval) was 0.82 (0.72-0.93). However, this association disappeared after the third dose (0.96 [0.78-1.18]). Of the dyslipidemia components, hypertriglyceridemia was inversely associated with SARS-CoV-2 spike IgG antibody titre after both the second and third doses (ratio of means: 0.82 [0.70-0.95] and 0.73 [0.56-0.95], respectively). In women, IgG titres did not differ according to dyslipidemia or hypertriglyceridemia status after either dose. CONCLUSIONS: These results suggest a detrimental role of hypertriglyceridemia in the humoral immune response to the BNT162b2 vaccine for COVID-19 in men but not in women.

Systematic Review and Meta-Analysis of Telecoaching for Self-Care Management among Persons with Type 2 Diabetes Mellitus.

BACKGROUND: In response to the need for safe care for people with diabetes mellitus in the current outbreak of COVID-19, it is critical to evaluate the model, service delivery, feasibility, and efficiency of diabetes mellitus telecoaching. OBJECTIVE: This study aimed to conduct a systematic review and meta-analysis of the model and efficacy of telecoaching to improve self-care and clinical outcomes. METHODS: This study uses the Preferred Reporting Item for Systematic Review and Meta-Analysis (PRISMA). We searched on 22 March 2022, using keywords that matched the MeSH browser in four databases to find relevant studies, namely, PubMed/Medline, Proquest, Scopus, and EBSCOhost. Additionally, we collected randomized controlled trials (RCTs) on Google Scholar using the snowball technique. A quality assessment was performed using the Cochrane Collaboration's Risk of Bias tool (RoB)2. The meta-analysis used the DerSimonian-Laird random-effects model to analyze the pooled mean difference (MD) and its p-value. RESULTS: Thirteen RCT studies were included for the systematic review and meta-analysis with a total number of participants of 3300. The model of telecoaching is a form of using nurses-led telephone and mobile apps, which are relatively cost-effective. The meta-analysis showed a positively improved statistically significance in clinical outcomes, including in HbA1c (a pooled MD of -0.33; 95% CI: -0.51--0.15; p = 0.0003), blood glucose (-18.99; 95% CI: -20.89--17.09; p = 0.00001), systolic blood pressure (-2.66; 95% CI: -3.66--1.66; p = 0.00001), body mass index (-0.79; 95% CI: -1.39--0.18; p = 0.01), and weight (-2.16 kg; 95% CI: -3.95--0.38; p = 0.02). It was not, however, statistically significant in diastolic blood pressure (-0.87; 95% CI: -2.02-0.28; p = 0.14), total cholesterol (-0.07; 95% CI: -0.26-0.12; p = 0.46), low-density lipoprotein (-2.19; 95% CI: -6.70-2.31; p = 0.34), triglycerides (-13.56; 95% CI: -40.46-13.35; p = 0.32) and high-density protein (0.40; 95% CI: -1.12-1.91; p = 0.61). CONCLUSIONS: The telecoaching with nurses-led telephone and mobile apps significantly affected clinical outcomes on HbA1c, systolic blood pressure, weight, and BMI. Moreover, there was no significant effect on the total cholesterol, low-density lipoprotein, triglycerides, and high-density lipoprotein. Thus, telecoaching has the potential as a care model in diabetes mellitus during COVID-19 and similar pandemics to improve self-care and clinical outcomes, but all the studies analyzed involved non-COVID-19 patients, limiting the generalizability of the results to COVID-19.

The anti-inflammatory effects of a Mediterranean diet: a review.

PURPOSE OF REVIEW: Chronic noncommunicable diseases remain the leading cause of morbidity and mortality worldwide and the majority are preventable with a healthy diet and lifestyle, but controversy remains as to the best approach. Greater adherence to a traditional Mediterranean diet has consistently been associated with lower morbidity and mortality from cardiovascular disease, diabetes and many cancers, and lower all-cause mortality. Despite the well known benefits on chronic disease risk there remains some scepticism as to the effects of this dietary pattern across populations outside the Mediterranean and the mechanisms of action of this traditional plant-based dietary pattern.This narrative review aims to summarize the latest evidence on the health protective effects of a traditional Mediterranean diet on chronic noncommunicable diseases, specifically focussing on the anti-inflammatory effects of this highly published dietary pattern. RECENT FINDINGS: Recent high-quality evidence now supports a Mediterranean diet in secondary prevention of cardiovascular disease with impacts on atherosclerosis progression, likely through reduction of systemic inflammation and irrespective of changes in cholesterol or weight. The Mediterranean diet has a low Dietary Inflammatory Index illustrating its anti-inflammatory potential. This dietary pattern beneficially modulates the gut microbiota and immune system, including emerging evidence for efficacy against severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019). Emerging evidence shows clinicians are not routinely recommending a Mediterranean diet despite well known evidence due to barriers such as lack of training, patient materials and concerns about potential patient adherence. SUMMARY: The physiological mechanisms of action of this healthy diet pattern are becoming better understood to be multisystem and involving the gut. Larger controlled trials investigating mechanistic effects in broader non-Mediterranean populations are warranted. Although reflected in therapeutic guidelines for chronic disease management worldwide there are individual, clinical practice and health system barriers to its implementation that need a multisectoral approach to address.