Modifiable Host Factors for the Prevention and Treatment of COVID-19: Diet and Lifestyle/Diet and Lifestyle Factors in the Prevention of COVID-19.

Many studies have shown that the immune system requires adequate nutrition to work at an optimal level. Not only do optimized nutritional strategies support the immune system, but they also reduce chronic inflammation. Nutritional supplements that are recommended for patients with critical illnesses are thought to also be effective for the coronavirus disease 2019 (COVID-19) patients in the intensive care unit. Some studies have recommended fresh fruits and vegetables, soy, nuts, and antioxidants, such as omega-3 fatty acids, to improve immune system activity. Although nutritional status is considered to be an important prognostic factor for patients with COVID-19, there is to date no sufficient evidence that optimal nutritional therapies can be beneficial for these patients. Some have argued that the COVID-19 pandemic is a good opportunity to test the effectiveness of nutritional intervention for infectious diseases. Many researchers have suggested that testing the proposed nutritional approaches for infectious diseases in the context of a pandemic would be highly informative. The authors of other review papers concluded that it is important to have a diet based on fresh foods, such as fruits, vegetables, whole grains, low-fat dairy products, and healthy fats (i.e., olive oil and fish oil), and to limit the intake of sugary drinks as well as high-calorie and high-salt foods. In this review, we discuss the clinical significance of functional food ingredients as complementary therapies potentially beneficial for the prevention or treatment of COVID-19. We believe that our review will be helpful to plan and deploy future studies to conclude these potentials against COVID-19, but also to new infectious diseases that may arise in the future.

Placental extracts regulate melanin synthesis in normal human melanocytes with alterations of mitochondrial respiration.

Placental extracts have been widely used as skin lightening agents in the Japanese cosmetic market. Here, we show that placental extracts contain factors that can decrease or increase melanin synthesis by normal human melanocytes in vitro in possible association with mitochondrial respiration. When normal human melanocytes were treated with a whole porcine placental extract, melanin synthesis was decreased. In contrast, a porcine placental extract in which exudates and insoluble materials including lipids had been removed increased melanin synthesis. In addition, the amount of tyrosinase, the enzyme critical for melanin synthesis, changed in accordance with the alteration of melanin synthesis. Interestingly, the amount of manganese-dependent superoxide dismutase (MnSOD), a mitochondrial-resident antioxidant enzyme, was increased when melanin synthesis was decreased by the whole placental extract. Mitochondrial respiration and glycolysis also changed following treatment with the placental extracts. These results suggest that placental extracts contain factors that can increase or decrease melanin synthesis by normal human melanocytes and that mitochondrial function may be associated with the placental extract-induced regulation of melanogenesis.

Human placental extract treatment for non-alcoholic steatohepatitis non-responsive to lifestyle intervention: A pilot study.

AIM: No pharmacological therapies have been established for non-alcoholic steatohepatitis (NASH), which can lead to liver-related mortality. Human placental extract (HPE), which has anti-inflammatory effects, has been expected to be a promising treatment for chronic liver disease. This pilot study was conducted to evaluate the efficacy of HPE for biopsy-diagnosed NASH. METHODS: After a lifestyle intervention for 12 weeks, 10 subjects with abnormal alanine aminotransferase (≥30 IU/L) and biopsy-proven NASH (Non-Alcoholic Fatty Liver Disease Activity Score [NAS], ≥4) received i.m. injections of HPE (Laennec) at a dose of 4 mL/day twice per week for 24 weeks, and seven of them underwent a second liver biopsy after the treatment. Liver biopsies were scored for NAS and fibrosis. Histological response was defined as a decrease of 2 points or more in NAS and no increase in fibrosis. RESULTS: Serum transaminase activities were significantly lower at 8 weeks compared with pretreatment levels in nine patients who continued treatment for 24 weeks. One patient refused to continue the treatment soon after starting therapies. In seven patients undergoing post-treatment biopsies, NAS (mean [standard deviation]) mildly decreased from 5.29 (0.95) to 4.00 (1.83) without reaching statistical significance (P = 0.078). Histological response was observed in all three obese patients and in only one of four non-obese ones. No significant changes were observed in body mass index, lipid profiles and diabetic control/insulin resistance. CONCLUSION: In NASH patients who received HPE treatment, significant reductions in serum liver enzymes were obtained after 8 weeks. Histological efficacy may be better in obese patients than in non-obese ones.

Lower circulating levels of dehydroepiandrosterone, independent of insulin resistance, is an important determinant of severity of non-alcoholic steatohepatitis in Japanese patients.

AIM: The biological basis of variability in histological progression of non-alcoholic fatty liver disease (NAFLD) remains unknown. Dehydroepiandrosterone (DHEA), the most abundant steroid hormone, has been shown to influence sensitivity to reactive oxygen species, insulin sensitivity and expression of peroxisome proliferator-activated receptor-α. Our aim was to determine whether more histologically advanced NAFLD is associated with low circulating levels of DHEA in Japanese patients. METHODS: Serum samples were obtained in 133 Japanese patients with biopsy-proven NAFLD and in 399 sex- and age-matched healthy people undergoing health checkups. Serum levels of sulfated DHEA (DHEA-S) were measured by chemiluminescent enzyme immunoassay. RESULTS: Serum DHEA-S levels in NAFLD patients were similar to those in the control group. Of 133 patients, 90 patients were diagnosed as non-alcoholic steatohepatitis (NASH): 73 patients had stage 0-2, and 17 had stage 3 or 4. Patients with advanced NAFLD (NASH with fibrosis stage 3 or 4) had lower plasma levels of DHEA-S than patients with mild NAFLD (simple steatosis or NASH with fibrosis stage 0-2). The area under the receiver operating characteristic curve for DHEA in separating patients with and without advanced fibrosis was 0.788. A "dose effect" of lower DHEA-S and incremental fibrosis stage was observed with a mean DHEA-S of 170.4 ± 129.2, 137.6 ± 110.5, 96.2 ± 79.3, 61.2 ± 46.3 and 30.0 ± 32.0 µg/dL for fibrosis stages 0, 1, 2, 3, and 4, respectively. The association between DHEA-S and severity of NAFLD persisted after adjusting for age, sex and insulin resistance. CONCLUSION: Low circulating DHEA-S might have a role in the development of advanced NASH.

Effects on the Human Body of a Dietary Supplement Containing L-Carnitine and Garcinia cambogia Extract: A Study using Double-blind Tests.

The effect of a dietary supplement with L-carnitine (600 mg/day) and Garcinia cambogia extract (500 mg/day as hydroxycitric acid) as main ingredients was studied in 35 healthy volunteers {48.3 +/- 6.9 years, body mass index (BMI): 26.3 +/- 1.7} in a double-blind test (18 subjects in the Test Group and 17 in the Control Group). The yearly examination includes the standard yearly medical tests done in Japan, tests for assessing hormonal age, and a survey for assessing physical and mental fitness of the subjects, called the Anti-Aging QOL Common Questionnaire (AAQol). Use of this supplement significantly improved the level of lipid peroxides (-12.8%) in the blood as well as physical symptoms such as "tired eyes," "blurry eyes," "muscle pain/stiffness," "early satiety," "epigastralgia," "dizziness," "arthralgia" and "easily breaking into a sweat." The Control Group showed a significantly favorable improvement rate, especially for "dizziness." On the other hand, groups of subjects using the test compounds saw a significant rise in total cholesterol (4.5%), fasting blood sugar (4.1%) and HbA1c (3.4%). Our findings suggest that the consumption of the supplement can reduce the oxidative damage; however, the effect on QOL was equivocal. Garcinia cambogia extract did not show dietary efficacy.

[Hormone replacement Up-to-date. Hormone replacement therapy in anti-aging medicine].

The purpose of anti-aging medicine is to raise quality of life (QOL) and to aim at healthy longevity. Melatonin, DHEA(-s) (dehydroepiandrosterone [sulfate]), somatotropin/IGF-I (insulin-like growth factor-I), male and female hormone decrease with aging, that can be prevented by hormone replacement therapy. This therapy has two sides of supplement of the deficit and a healthy increase. Hormone age is "the function age that expressed whether you are equivalent to a hormone secretion state of how old average" and 30 years old or 70-80% of chronological age regard the targeted value of hormone age. We do not decide quantity of hormone replacement uniformly. The reasonable quantity should be determined based on each figure, active mass, life level, and/or blood levels of hormones. Data accumulation for a long term in multiple institutions is important.

A novel missense mutation in a Japanese patient with gelatinous droplike corneal dystrophy.

PURPOSE: To report a novel missense mutation in TACSTD2 gene, L186P, responsible for gelatinous droplike dystrophy (GDLD). DESIGN: Case report and experimental study. METHOD: A 10-year-old Japanese boy suffering from typical GDLD was studied. A 1.1-kb DNA fragment of the TACSTD2 gene was amplified and analyzed using a molecular biological method. cDNA from the patient's cornea was also analyzed to determine which allele was expressed in the patient's corneal epithelium. RESULTS: Sequence analysis revealed that the patient is a compound heterozygote for the Q118X mutation and the L186P, the first missense mutation found in Japanese GDLD. Polymerase chain reaction-restriction fragment length polymorphism analysis from cDNA of patient's cornea revealed that the L186P missense mutation allele is expressed in the patient's corneal epithelium. CONCLUSION: We describe a novel mutation in one case of Japanese GDLD. The results confirm that the missense mutation L186P in the TACSTD2 gene is also responsible for the GDLD phenotype.

The clinical role of N-isopropyl-p-[123I]-iodoamphetamine single photon emission computed tomography in the follow-up of choroidal melanoma after radiotherapy.

BACKGROUND: Single photon emission computed tomography (SPECT) images with N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) have recently been used for the sensitive and specific detection of melanoma. CASES: Using 123I-IMP SPECT, we observed three patients over a period of 18 months in whom choroidal melanoma had been diagnosed. Two underwent radiotherapy (cyber knife) in our clinic; the other patient was referred to us after 8 months of proton beam irradiation at another clinic. OBSERVATIONS: In two of the three cases, no metastasis or tumor recurrence has been observed up to the present time. In these individuals, the average 123I-IMP uptake in the pathological eye gradually and progressively decreased after radiotherapy to levels seen in the fellow eye. One eye of the three patients examined here, however, exhibited tumor recurrence in the ciliary body as well as hepatic metastasis 12 months after radiation treatment. In the pathological eye of this patient, the average 123I-IMP uptake gradually decreased, but never reached the levels in the fellow eye during the observation period. CONCLUSIONS: 123I-IMP SPECT is a useful examination method not only for diagnosis but also for the follow-up of patients with choroidal melanoma.

Diagnosing dry eye using a blue-free barrier filter.

PURPOSE: To investigate the benefit of the blue-free barrier filter (BF filter) in diagnosing dry eye. DESIGN: Nonrandomized clinical comparison. METHODS: Fifty-three eyes with Sjögren syndrome (n = 42) or keratoconjunctivitis sicca (n = 11) were enrolled. Fluorescein staining was performed in temporal and nasal conjunctiva, and staining was scored with (BF score) and without the filter (FL score) from 0 to 3. Rose bengal staining was also scored (RB score) similarly. RESULTS: With FL scores of 0, 1, or 2, the BF score was significantly higher: 0.85 +/- 0.37 (P =.031), 1.74 +/- 0.65 (P =.001), and 2.65 +/- 0.48 (P =.001), respectively; with a FL score of 3, the BF score was 3 at all sites. The BF score was superior to the FL score in 66.6% of cases when the FL score was 0 and 1 and in 65.2% when the FL score was 2, but not when the FL score was 3. When the RB score was 0, 1, or 2, the BF score was higher: 1.88 +/- 0.92, 1.78 +/- 0.79, and 2.57 +/- 0.50, respectively (P =.001 for all); when the RB score was 3, the BF score was 2.97 +/- 0.16. The BF score was superior to the RB score in 75.5% of cases when the RB score was 0 and 1 and in 57.8% when the FL score was 2, but not in cases with a RB score of 3. CONCLUSIONS: The BF filter detects damaged conjunctival epithelium stained with fluorescein. Using the filter was beneficial in mild-to-moderate cases, not in severe cases. The BF filter allows diagnosis of dry eye even at the initial stage that is undetectable by conventional observation.

Electron microscopy of the epithelial flap created by ethanol treatment in the rabbit corneal epithelium.

PURPOSE: To assess the effect of corneal debridement with 25% ethanol on rabbit corneal epithelium by electron microscopy. SETTING: Department of Ophthalmology, Osaka University School of Medicine, Osaka, Japan. METHODS: Rabbit corneas were deepithelialized by applying 25% ethanol for 3 minutes, and a hinged epithelial flap was created and repositioned. Ten corneas were evaluated immediately after the epithelial debridement procedure and at 1, 3, and 7 days. Histological changes were evaluated using scanning and transmission electron microscopy. RESULTS: Corneas treated with ethanol showed a decrease in microvilli, breaks in intercellular junctions, epithelial cell edema, and damage in basement membrane hemidesmosomes. These toxic changes recovered to an almost normal appearance after 24 hours and rapidly improved over the following week. An increase in desquamated cells was observed after debridement; this returned to normal after 1 week according to the normal cellular cycle. Wing cells showed no damage at any stage. CONCLUSIONS: Although ethanol appeared to have a toxic effect on rabbit epithelial cells, the effect did not persist over time. The first signs of recovery were observed 24 hours after debridement, and full recovery was observed over the following week. The ethanol path to the central basement membrane appeared to be centripetally from a round cut through the basement membrane, leaving the wing cells intact.

Retinal glial cells stimulate microvascular pericyte proliferation via fibroblast growth factor and platelet-derived growth factor in vitro.

PURPOSE: To investigate whether retinal glial cells (RGCs), which are believed to play an important role in the development and maintenance of microvessels, stimulate the proliferation of retinal bovine microvascular pericytes, an essential component of the vessels. METHODS: Conditioned medium (CM) was collected from a primary culture of RGC obtained from chick embryonic retina. The cell number was assayed after stimulation by RGC-CM. Also, by neutralizing antibody and reverse transcription polymerase chain reaction (RT-PCR), we tried to identify which factor of the RGCs contributes to the pericyte stimulation. RESULTS: Pericyte proliferation was stimulated by RGC-CM in a dose-dependent manner. Platelet-derived growth factor-BB (PDGF-BB), acidic fibroblast growth factor (aFGF), and basic fibroblast growth factor (bFGF) stimulated pericyte proliferation; however, PDGF-AA, transforming growth factor-beta2 (TGF-beta2), and vascular endothelial growth factor (VEGF) did not. The RGC-CM-dependent stimulative effect was blocked, in part, by the neutralizing antibodies for aFGF, bFGF, and PDGF. A mixture of these three antibodies completely blocked the stimulation. RT-PCR revealed that RNA for aFGF, bFGF, and TGF-beta2 were expressed in RGCs. CONCLUSIONS: Pericyte growth is stimulated in vitro by RGC-CM through aFGF, bFGF, PDGF-BB, at least in part. This finding suggests that RGCs may modulate in vivo pericyte cell growth through these three growth factors.