Evidence of the interactions between immunosuppressive drugs used in autoimmune rheumatic diseases and Chinese herbal medicine: A scoping review.

OBJECTIVES: Chinese herbal medicine (CHM) has been shown to be effective in autoimmune rheumatic diseases, but harmful herb-drug interactions might be inherent. We aim to review the evidence regarding herb-drug interactions between immunosuppressive drugs used in autoimmune rheumatic diseases and CHM. METHODS: We searched PubMed, EMBASE and CINAHL from inception till 30 April 2023 using keywords that encompassed 'herb-drug interactions', 'herbs' and 'immunosuppressants'. Articles were included if they contained reports about interactions between immunosuppressive drugs used in the treatment of rheumatic diseases with CHM. Level of evidence for each pair of interaction was graded using the algorithm developed by Colalto. RESULTS: A total of 65 articles and 44 unique pairs of interactions were identified. HDIs were reported for cyclophosphamide, cyclosporine, tacrolimus, methotrexate, mycophenolic acid, glucocorticoids, sulfasalazine, tofacitinib and biologic disease-modifying antirheumatic drugs. Among these, cyclosporine (n = 27, 41.5%) and tacrolimus (n = 19, 29.2%) had the highest number of documented interactions. Hypericum perforatum had the highest level of evidence of interaction with cyclosporine and tacrolimus. Consumption reduced the bioavailability and therapeutic effects of the drugs. Schisandra sphenanthera had the highest level of evidence of interaction with tacrolimus and increased the bioavailability of the drug. Majority of the articles were animal studies. CONCLUSION: Overall level of evidence for the included studies were low, though interactions between cyclosporine, tacrolimus, Hypericum perforatum and Schisandra sphenanthera were the most and well-documented. Healthcare professionals should actively enquire about the concurrent use of CHM in patients, especially when drugs with a narrow therapeutic index are consumed.

Induction of ferroptosis and apoptosis in endometrial cancer cells by dihydroisotanshinone I.

Danshen, also known as Salvia miltiorrhiza, is a medicinal herb used in traditional Chinese medicine. Its potential impact on endometrial cancer has not been thoroughly investigated. This study aimed to examine the effect of dihydroisotanshinone I (DT), a compound found in Danshen, on the viability of ARK1 and ARK2 endometrial cancer cells and its mechanisms. The results showed that 10 µM DT inhibited cell viability of ARK1 and ARK2 cells by inducing apoptosis and ferroptosis, which was achieved by blocking the expression of GPX4. In vivo experiments using a xenograft nude mouse model indicated that DT treatment significantly reduced tumor volume without causing any adverse effects. These findings suggest that DT may be a potential therapeutic agent for inhibiting endometrial cancer cell viability, but further research is needed to confirm these results.

Rice GA3ox1 modulates pollen starch granule accumulation and pollen wall development.

The rice GA biosynthetic gene OsGA3ox1 has been proposed to regulate pollen development through the gametophytic manner, but cellular characterization of its mutant pollen is lacking. In this study, three heterozygotic biallelic variants, "-3/-19", "-3/-2" and "-3/-10", each containing one null and one 3bp-deletion allele, were obtained by the CRISPR/Cas9 technique for the functional study of OsGA3ox1. The three homozygotes, "-19/-19", "-2/-2" and "-10/-10", derived from heterozygotic variants, did not affect the development of most vegetative and floral organs but showed a significant reduction in seed-setting rate and in pollen viability. Anatomic characterizations of these mutated osga3ox1 pollens revealed defects in starch granule accumulation and pollen wall development. Additional molecular characterization suggests that abnormal pollen development in the osga3ox1 mutants might be linked to the regulation of transcription factors OsGAMYB, OsTDR and OsbHLH142 during late pollen development. In brief, the rice GA3ox1 is a crucial gene that modulates pollen starch granule accumulation and pollen wall development at the gametophytic phase.

The anti-SARS-CoV-2 effect and mechanism of Chiehyuan herbal oral protection solution.

The Chiehyuan herbal oral protection solution (GB-2) is a herbal mixture commonly utilized in Taiwan for combating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as per traditional Chinese medicine practices. This study assessed the clinical impact of GB-2 through prospective clinical trials. With twice-daily use for a week, GB-2 was shown to diminish the expression of angiotensin-converting enzyme 2 (ACE2) in oral mucosal cells. Moreover, after two weeks of use, it could reduce transmembrane protease, serine 2 (TMRPSS2) expression in these cells. Additionally, in vitro experiments demonstrated that GB-2 lessened the entry efficiency of the Omicron, L452R-D614G, T478K-D614G, and L452R-T478K-D614G variants of the SARS-CoV-2 pseudotyped lentivirus. It also impeded the interaction between ACE2 and the receptor-binding domain (RBD) presenting N501Y-K417N-E484A-G339D-Q493R-G496S-Q498R and L452R-T478K mutations. Glycyrrhizic acid, a major compound in GB-2, also hindered the entry of the Omicron variant (BA.1) of the SARS-CoV-2 pseudotyped lentivirus by obstructing the binding between ACE2 and the RBD presenting the N501Y-K417N-E484A-G339D-Q493R-G496S-Q498R mutation. To sum up, these findings suggest that GB-2 can decrease ACE2 and TMPRSS2 expression in oral mucosal cells. Both glycyrrhizic acid and GB-2 were found to reduce the entry efficiency of the Omicron variant (BA.1) of the SARS-CoV-2 pseudotyped lentivirus and block the binding between ACE2 and the RBD with the N501Y-K417N-E484A-G339D-Q493R-G496S-Q498R mutation. This evidence implies that GB-2 might be a potential candidate for further study as a preventative measure against SARS-CoV-2 infection.

Steroidal constituents from Solanum nigrum.

Three previously undescribed steroidal constituents including two sterols (1-2) and one pregnane-type steroidal glycoside (6), along with nineteen known ones (3-5, 7-22), were isolated from the 80% alcohol extraction of Solanum nigrum L. Their structures and the absolute configurations were established by analysis of the extensive spectroscopic data (1H/13 NMR, 1H1H COSY, HSQC, HMBC, and NOESY), and/or by comparisons of the experimental electronic circular dichroism (ECD) spectra with those calculated ones by TDDFT method. Further, a MTT assay was applied to demonstrate that compounds 1-4, 6-12, 18, and 22 exhibited significant cytotoxic activities against SW480 cells, and compounds 1-4, 6-14, and 16-22 showed significant cytotoxic activities against Hep3B cells.

Post-surgery interventions for hip fracture: a systematic review of randomized controlled trials.

BACKGROUND: Interventions provided after hip fracture surgery have been shown to reduce mortality and improve functional outcomes. While some systematic studies have evaluated the efficacy of post-surgery interventions, there lacks a systematically rigorous examination of all the post-surgery interventions which allows healthcare providers to easily identify post-operative interventions most pertinent to patient's recovery. OBJECTIVES: We aim to provide an overview of the available evidence on post-surgery interventions provided in the acute, subacute and community settings to improve outcomes for patients with hip fractures. METHODS: We performed a systematic literature review guided by the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA). We included articles that were (1) randomized controlled trials (RCTs), (2) involved post-surgery interventions that were conducted in the acute, subacute or community settings and (3) conducted among older patients above 65 years old with any type of non-pathological hip fracture that was surgically treated, and who were able to walk without assistance prior to the fracture. We excluded (1) non-English language articles, (2) abstract-only publications, (3) articles with only surgical interventions, (4) articles with interventions that commenced pre-surgery or immediately upon completion of surgery or blood transfusion, (5) animal studies. Due to the large number of RCTs identified, we only included "good quality" RCTs with Jadad score ≥ 3 for data extraction and synthesis. RESULTS: Our literature search has identified 109 good quality RCTs on post-surgery interventions for patients with fragility hip fractures. Among the 109 RCTs, 63% of the identified RCTs (n = 69) were related to rehabilitation or medication/nutrition supplementation, with the remaining RCTs focusing on osteoporosis management, optimization of clinical management, prevention of venous thromboembolism, fall prevention, multidisciplinary approaches, discharge support, management of post-operative anemia as well as group learning and motivational interviewing. For the interventions conducted in inpatient and outpatient settings investigating medication/nutrition supplementation, all reported improvement in outcomes (ranging from reduced postoperative complications, reduced length of hospital stay, improved functional recovery, reduced mortality rate, improved bone mineral density and reduced falls), except for a study investigating anabolic steroids. RCTs involving post-discharge osteoporosis care management generally reported improved osteoporosis management except for a RCT investigating multidisciplinary post-fracture clinic led by geriatrician with physiotherapist and occupational therapist. The trials investigating group learning and motivational interviewing also reported positive outcome respectively. The other interventions yielded mixed results. The interventions in this review had minor or no side effects reported. CONCLUSIONS: The identified RCTs regarding post-surgery interventions were heterogeneous in terms of type of interventions, settings and outcome measures. Combining interventions across inpatient and outpatient settings may be able to achieve better outcomes such as improved physical function recovery and improved nutritional status recovery. For example, nutritional supplementation could be made available for patients who have undergone hip fracture surgery in the inpatient settings, followed by post-discharge outpatient osteoporosis care management. The findings from this review can aid in clinical practice by allowing formulation of thematic program with combination of interventions as part of bundled care to improve outcome for patients who have undergone hip fracture surgery.

Signals and Their Perception for Remodelling, Adjustment and Repair of the Plant Cell Wall.

The integrity of the cell wall is important for plant cells. Mechanical or chemical distortions, tension, pH changes in the apoplast, disturbance of the ion homeostasis, leakage of cell compounds into the apoplastic space or breakdown of cell wall polysaccharides activate cellular responses which often occur via plasma membrane-localized receptors. Breakdown products of the cell wall polysaccharides function as damage-associated molecular patterns and derive from cellulose (cello-oligomers), hemicelluloses (mainly xyloglucans and mixed-linkage glucans as well as glucuronoarabinoglucans in Poaceae) and pectins (oligogalacturonides). In addition, several types of channels participate in mechanosensing and convert physical into chemical signals. To establish a proper response, the cell has to integrate information about apoplastic alterations and disturbance of its wall with cell-internal programs which require modifications in the wall architecture due to growth, differentiation or cell division. We summarize recent progress in pattern recognition receptors for plant-derived oligosaccharides, with a focus on malectin domain-containing receptor kinases and their crosstalk with other perception systems and intracellular signaling events.

Hernandezine induces autophagic cell death in human pancreatic cancer cells via activation of the ROS/AMPK signaling pathway.

Hernandezine (Her) is a bisbenzylisoquinoline alkaloid extracted from the traditional Chinese herbal medicine Thalictrum glandulosissimum. Evidence shows that Her is a natural agonist of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and induces apoptosis and autophagy in tumor cells. In this study, we investigated the role of autophagy in Her-induced cell death in human pancreatic cancer cell lines. We showed that Her dose-dependently suppressed cell proliferation, promoted autophagy and induced autophagic death in pancreatic ductal adenocarcinoma (PDAC) cell lines Capan-1 and SW1990. The IC50 values of Her in inhibition of Capan-1 and SW1990 cells were 47.7 µM and 40.1 µM, respectively. Immunoblotting showed that Her (1-40 µM) promoted the conversion of LC3-I to LC3-II, and Her exerted concentration-dependent and time-dependent effects on autophagy activation in PDAC cells. In transmission electron microscopy and fluorescence image analysis, we found that autophagic vacuoles were significantly increased in Her-treated cells. Knockdown of ATG5, a key gene in the autophagy pathway, alleviated the activation of autophagy by Her. These results demonstrated that Her induced autophagy in PDAC cells. Intensely activated autophagy could promote cell death. The autophagy inhibitors, BafA1 and HCQ significantly inhibited Her-induced cell death, implying that Her induced autophagic cell death in PDAC cells. Moreover, we showed that Her activated autophagy by increasing the phosphorylation of AMPK and decreasing the phosphorylation of mTOR/p70S6K. Knockdown of AMPKα relieves the autophagic cell death induced by Her. Furthermore, Her concentration-dependently enhanced reactive oxygen species (ROS) generation in PDAC cells. Antioxidants could reduce the phosphorylation of AMPK and suppress autophagic cell death induced by Her. Our study provides evidence for the development of Her as a therapeutic agent for the treatment of pancreatic cancer.

In vivo efficiency of praziquantel treatment of single-sex Schistosoma japonicum aged three months old in mice.

Schistosomiasis is a major neglected tropical disease mainly caused by Schistosoma haematobium, S. japonicum and S. mansoni, and results in the greatest disease burden. Mass drug administration (MDA) with praziquantel (PZQ), a single drug only available for the disease, has played a vital role in schistosomiasis control. Therefore, any possibility of selection of the parasites for PZQ resistance or low sensitivity may hamper the 2030's target of global disease elimination. We had experimentally demonstrated the long-term survival and reproductive potential of single-sex (of either sex) S. japonicum infections in definitive hosts mice. What has not yet been adequately addressed is whether the long live single-sex schistosomes remain sensitive to PZQ, and what reproduction potential for those schistosomes surviving treatment may have. We therefore performed experimental mice studies to explore the treatment effectiveness of PZQ (at total doses of 200 or 400 mg/kg, corresponding to the sub-standard or standard treatment doses in humans) for single-sex S. japonicum aged three months old. The results showed that no treatment efficiency was observed on female schistosomes, whereas on male schistosomes only at PZQ 400 mg/kg a significant higher efficiency in reducing worm burdens was observed. Moreover, either schistosome males or females surviving PZQ treatment remained their reproduction potential as normal. The results indicate that long (i.e., three months) live single-sex S. japonicum can easily survive the current treatment strategy, and moreover, any schistosomes, if with PZQ resistance or low sensitivity, could be easily transmitted in nature. Therefore, in order to realize the target for the national and the global schistosomiasis elimination, there is undoubtedly a great need for refining PZQ administration and dosage, looking for alternative therapies, and/or developing vaccines against schistosome.

Revealing and modeling of fire products in gas-phase for epoxy/black phosphorus-based nanocomposites.

This work aims at revealing and optimizing the mechanism, to promote the design of phosphorus-based flame retardants (PFRs) for controlling the spread of fire risk caused by the continuous spread of polymers. Herein, we synthesized about 10 nm TiO2 grown in situ on the surface of BP through a simple hydrothermal procedure to introduce it into epoxy (EP/BP-TiO2). In the first place, EP/BP-TiO22.0 nanocomposite achieves a reduction of 58.96% and 50.35% in PHRR and THR, respectively. Secondly, the pyrolysis of BP from Pn to P4, P3 and P2 is revealed. As a guide, P4 is established as a characteristic product of the analytical model for evaluating the effects in the gas phase for BP-based hybrids. Finally, this work clarifies the enhancement path for BP-TiO2 is optimized for the capturing of OH· and H· radicals by P4(POx). Crucially, this study reveals and controls the mechanism of the BP-based hybrids at the molecular level, which is expected to provide a promising analytical model for broad market PFRs design to address the risks and challenges of casualties and ecology caused by composites fire.

Dietary chlorella (Chlorella vulgaris) supplementation effectively improves body color, alleviates muscle inflammation and inhibits apoptosis in largemouth bass (Micropterus salmoides).

Muscle quality, antioxidant status, and inflammatory and apoptotic molecule expression were investigated in juvenile largemouth bass fed five levels of Chlorella for 60 days. The results showed that muscle quality can be improved by increasing the muscle crude protein content, muscle and skin brightness value (L*), redness value (a*) and yellowness value (b*) in Chlorella-supplemented diets without affecting the growth and muscle fiber development of fish. Chlorella supplementation did not cause oxidative stress in muscle, but optimal Chlorella administration alleviated the muscle inflammatory response by downregulating the nuclear factor κB (NF-κB)-mediated proinflammatory factors such as interleukin 1ß (IL-1ß) and interleukin 8 (IL-8). Moreover, anti-apoptotic effects were induced by upregulation of anti-apoptotic genes, such as b cell lymphoma-2 (bcl-2) and myeloid cell leukemia-1 (mcl-1), and downregulation of pro-apoptotic genes, including bcl2-associated x (bax) and caspase3. In conclusion, Chlorella improved muscle quality, alleviated muscle inflammation and resisted muscle apoptosis.

Emergency department utilisation among older adults-Protocol for a systematic review of determinants and conceptual frameworks.

BACKGROUND: Older adults aged 65 years and above have a disproportionately higher utilization of emergency healthcare, of which Emergency Department (ED) visits are a key component. They experience higher degree of multimorbidity and mobility issues compared to younger patients, and are consequently more likely to experience a health event which requires an ED visit. During their visit, older adults tend to require more extensive workup, therefore spending a greater amount of time in the ED. Compared to the younger population, older adults are more susceptible to adverse events following discharge. Considering these factors, investigating the determinants of ED utilisation would be valuable. In this paper, we present a protocol for a systematic review of the determinants of ED utilisation among communitydwelling older adults aged 65 years and above, applying Andersen and Newman's model of healthcare utilisation. Furthermore, we aim to present other conceptual frameworks for healthcare utilisation and propose a holistic approach for understanding the determinants of ED utilisation by older persons. METHODS: The protocol is developed in accordance with the standards of Campbell Collaboration guidelines for systematic reviews, with reference to the Cochrane Handbook for Systematic Review of Interventions. Medline, Embase and Scopus will be searched for studies published from 2000 to 2020. Studies evaluating more than one determinant for ED utilisation among older adults aged 65 years and above will be included. Search process and selection of studies will be presented in a PRISMA flow chart. Statistically significant (p < 0.05) determinants of ED utilisation will be grouped according to individual and societal determinants. Quality of the studies will be assessed using Newcastle Ottawa Scale (NOS). DISCUSSION: In Andersen and Newman's model, individual determinants include predisposing factors, enabling and illness factors, and societal determinants include technology and social norms. Additional conceptual frameworks for healthcare utilisation include Health Belief Model, Social Determinants of Health and Big Five personality traits. By incorporating the concepts of these models, we hope to develop a holistic approach of conceptualizing the factors that influence ED utilisation among older people. SYSTEMATIC REVIEW REGISTRATION: This protocol is registered on 8 May 2021 with PROSPERO's International Prospective Register of Systematic Reviews (CRD42021253770).

Determinants of emergency department utilisation by older adults in Singapore: A systematic review.

INTRODUCTION: Adults aged ≥60 years contribute to disproportionately higher visits to the emergency departments (ED). We performed a systematic review to examine the reasons why older persons visit the ED in Singapore. METHODS: We searched Medline, Embase and Scopus from January 2000 to December 2021 for studies reporting on ED utilisation by older adults in Singapore, and included studies that investigated determinants of ED utilisation. Statistically significant determinants and their effect sizes were extracted. Determinants of ED utilisation were organised using Andersen and Newman's model. Quality of studies was evaluated using Newcastle Ottawa Scale and Critical Appraisal Skills Programme. RESULTS: The search yielded 138 articles, of which 7 were used for analysis. Among the significant individual determinants were predisposing (staying in public rental housing, religiosity, loneliness, poorer coping), enabling (caregiver distress from behavioural and psychological symptoms of dementia) and health factors (multimorbidity in patients with dementia, frailty, primary care visit in last 6 months, better treatment adherence). The 7 included studies are of moderate quality and none of them employed conceptual frameworks to organise determinants of ED utilisation. CONCLUSION: The major determinants of ED utilisation by older adults in Singapore were largely individual factors. Evaluation of societal determinants of ED utilisation was lacking in the included studies. There is a need for a more holistic examination of determinants of ED utilisation locally based on conceptual models of health seeking behaviours.

Enzyme Activity of Natural Products on Cytochrome P450.

Drug-metabolizing enzymes, particularly the cytochrome P450 (CYP450) monooxygenases, play a pivotal role in pharmacokinetics. CYP450 enzymes can be affected by various xenobiotic substrates, which will eventually be responsible for most metabolism-based herb-herb or herb-drug interactions, usually involving competition with another drug for the same enzyme binding site. Compounds from herbal or natural products are involved in many scenarios in the context of such interactions. These interactions are decisive both in drug discovery regarding the synergistic effects, and drug application regarding unwanted side effects. Herein, this review was conducted as a comprehensive compilation of the effects of herbal ingredients on CYP450 enzymes. Nearly 500 publications reporting botanicals' effects on CYP450s were collected and analyzed. The countries focusing on this topic were summarized, the identified herbal ingredients affecting enzyme activity of CYP450s, as well as methods identifying the inhibitory/inducing effects were reviewed. Inhibitory effects of botanicals on CYP450 enzymes may contribute to synergistic effects, such as herbal formulae/prescriptions, or lead to therapeutic failure, or even increase concentrations of conventional medicines causing serious adverse events. Conducting this review may help in metabolism-based drug combination discovery, and in the evaluation of the safety profile of natural products used therapeutically.

Saikosaponin a promotes sleep by decreasing neuronal activities in the lateral hypothalamus.

Insomnia is one of the most prevalent sleep disorders, which imparts tremendous societal and economic impact. However, the present pharmacotherapy is greatly limited by adverse effects, so it is necessary to explore new drugs for the treatment of insomnia. Radix Bupleuri (RB) has been widely used in traditional Chinese medicine for >2000 years; it has many pharmacological effects, including sedation and anticonvulsant properties. The present study investigated the effects of saikosaponin a (SSa), an active component of RB, on sleep and locomotion. Male C57BL/6j mice received intraperitoneal injections of SSa at three different dosages (0.625, 1.25, and 2.5 mg/kg). Sleep parameters were analysed by electroencephalography and electromyography. The open-field test was used to measure locomotor activities. Our present results showed that SSa treatment significantly increased the duration of non-rapid eye movement sleep and shortened sleep latency in a dose-dependent manner. A high dose of SSa (2.5 mg/kg) also decreased locomotor activities. Moreover, by measuring c-Fos expression and the calcium signal in the lateral hypothalamus (LH), we found that SSa treatment decreased neuronal activity in the LH. In conclusion, SSa might be the sleep-promoting component in RB and its mechanism may be related to the modulation of neuronal activity in the LH.

Determinants of emergency department utilisation by older adults in Singapore: A systematic review

INTRODUCTION@#Adults aged ≥60 years contribute to disproportionately higher visits to the emergency departments (ED). We performed a systematic review to examine the reasons why older persons visit the ED in Singapore.@*METHODS@#We searched Medline, Embase and Scopus from January 2000 to December 2021 for studies reporting on ED utilisation by older adults in Singapore, and included studies that investigated determinants of ED utilisation. Statistically significant determinants and their effect sizes were extracted. Determinants of ED utilisation were organised using Andersen and Newman's model. Quality of studies was evaluated using Newcastle Ottawa Scale and Critical Appraisal Skills Programme.@*RESULTS@#The search yielded 138 articles, of which 7 were used for analysis. Among the significant individual determinants were predisposing (staying in public rental housing, religiosity, loneliness, poorer coping), enabling (caregiver distress from behavioural and psychological symptoms of dementia) and health factors (multimorbidity in patients with dementia, frailty, primary care visit in last 6 months, better treatment adherence). The 7 included studies are of moderate quality and none of them employed conceptual frameworks to organise determinants of ED utilisation.@*CONCLUSION@#The major determinants of ED utilisation by older adults in Singapore were largely individual factors. Evaluation of societal determinants of ED utilisation was lacking in the included studies. There is a need for a more holistic examination of determinants of ED utilisation locally based on conceptual models of health seeking behaviours.

In vivo and in vitro antiproliferative and antimetastatic effects of hemolymph of Aspongopus chinensis Dallas on breast cancer cell.

OBJECTIVE: To investigate the effects of Aspongopus（A.）chinensis hemolymph on the proliferation and metastasis of breast cancer cells. METHODS: The in vitro effects of A. chinensis hemolymph were investigated in murine (4T1) and human (HCC1937) breast cancer cell lines. Cytotoxicity, cell apoptosis, and cell migration were evaluated by using the cell counting kit-8 assay, Hoechst staining, and wound healing experiments, respectively. A syngeneic mouse model was established to evaluate the in vivo effects of the hemolymph extract on tumor growth and metastasis. Mouse body weight, tumor size, blood levels of function-related enzymes, and pathological features of the liver and kidney tissues were evaluated. RESULTS: The hemolymph of A. chinensis significantly inhibited in vitro tumor cell migration and viability while inducing apoptosis. Furthermore, it inhibited in vivo tumor growth and metastasis with a minimal effect on mouse body weight, and did not induce liver or kidney damage. CONCLUSION: Our results suggested that the A.chinensis hemolymph has antitumorigenic properties, suggesting it has potential as a novel therapeutic option for the treatment of metastatic breast cancer.

COVID-19 lockdown measures induced severe iron-deficiency anaemia resulting in central retinal vein occlusion and amenorrhea.

During the COVID-19 pandemic, precautionary measures taken by various countries include individual movement restrictions causing significant lifestyle changes and affecting dietary patterns. A 23-year-old woman presented with reduced left eye vision over 1 week and amenorrhea for 4 months. She was diagnosed with severe iron-deficiency anaemia causing central retinal vein occlusion and amenorrhea. During the lockdown, there was a change in her diet with greatly reduced iron intake. Iron is an essential mineral for retina metabolism and function. Iron supplementation was done with improvement in her vision. This case demonstrates the potential impact of lockdown measures on nutrition and health. Education of the general population on maintaining appropriate nutrition during periods of movement restriction is important and that nutritional evaluation and supplementation should be considered in patients with drastic changes in dietary pattern.

GB-2 blocking the interaction between ACE2 and wild type and mutation of spike protein of SARS-CoV-2.

Since the start of the outbreak of coronavirus disease 2019 in Wuhan, China, there have been more than 150 million confirmed cases of the disease reported to the World Health Organization. The beta variant (B.1.351 lineage), the mutation lineages of SARS-CoV-2, had increase transmissibility and resistance to neutralizing antibodies due to multiple mutations in the spike protein. N501Y, K417N and E484K, in the receptor binding domain (RBD) region may induce a conformational change of the spike protein and subsequently increase the infectivity of the beta variant. The L452R mutation in the epsilon variant (the B.1.427/B.1.429 variants) also reduced neutralizing activity of monoclonal antibodies. In this study, we discovered that 300 µg/mL GB-2, from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit the binding between ACE2 and wild-type (Wuhan type) RBD spike protein. GB-2 can inhibit the binding between ACE2 and RBD with K417N-E484K-N501Y mutation in a dose-dependent manner. GB-2 inhibited the binding between ACE2 and the RBD with a single mutation (K417N or N501Y or L452R) except the E484K mutation. In the compositions of GB-2, glycyrrhiza uralensis Fisch. ex DC., theaflavin and (+)-catechin cannot inhibit the binding between ACE2 and wild-type RBD spike protein. Theaflavin 3-gallate can inhibit the binding between ACE2 and wild-type RBD spike protein. Our results suggest that GB-2 could be a potential candidate for the prophylaxis of some SARS-CoV-2 variants infection in the further clinical study because of its inhibition of binding between ACE2 and RBD with K417N-E484K-N501Y mutations or L452R mutation.

Ginsenosides Rb2 and Rd2 isolated from Panax notoginseng flowers attenuate platelet function through P2Y12-mediated cAMP/PKA and PI3K/Akt/Erk1/2 signaling.

Saponins derived from Panax notoginseng root are widely used as herbal medicines and dietary supplements due to their wide range of health benefits. However, the effects of those from Panax notoginseng flowers (PNF) on platelet function and thrombus formation remain largely unknown. Using a series of platelet function assays, we found that G-Rb2 and G-Rd2, among the ten PNF saponin monomers, significantly inhibited human platelet aggregation and activation induced by adenosine diphosphate (ADP) in vitro. The 50% inhibitory concentration (IC50) of G-Rb2 and G-Rd2 against ADP-induced platelet aggregation was 85.5 ± 4.5 µg mL-1 and 51.4 ± 4.6 µg mL-1, respectively. Mechanistically, G-Rb2 and G-Rd2 could effectively modulate platelet P2Y12-mediated signaling by up-regulating cAMP/PKA signaling and down-regulating PI3K/Akt/Erk1/2 signaling pathways. Co-incubation of the P2Y12 antagonist cangrelor with either G-Rb2 or G-Rd2 did not show significant additive inhibitory effects. G-Rb2 and G-Rd2 also substantially suppressed thrombus growth in a FeCl3-induced murine arteriole thrombosis model in vivo. Interestingly, G-Rd2 generally exhibited more potent inhibitory effects on platelet function and thrombus formation than G-Rb2. Thus, our data suggest that PNF-derived G-Rb2 and G-Rd2 effectively attenuate platelet hyperactivity through modulating signaling pathways downstream of P2Y12, which indicates G-Rb2 and G-Rd2 may play important preventive roles in thrombotic diseases.