Immune system aging (immune senescence) is an important factor contributing to the increased incidence and mortality rates among the elderly. Immune senescence, characterized by a decline in immune function, can also lead to aging and tissue dysfunction in organs as well as the lymphatic system. This suggests that aged immune cells may contribute to systemic aging. Conversely, transplantation of young immune cells into aged mice has been shown to improve systemic aging traits, indicating that immune system senescent cells could be a significant therapeutic target for promoting healthy aging. However, the molecular mechanisms behind immune senescence are not fully understood. Advances in unraveling these molecular processes are expected to lead to the discovery of new methods for preventing aging and extending lifespan.

Purpose: Angiogenesis inhibitor therapy for cancer is an efficient treatment as a "starvation tactic" against tumor tissues. Angiogenesis inhibitors, such as bevacizumab (avastin), a Vascular endothelial growth factor A (VEGF-A) inhibitor, and ramucirumab, a VEGF-A receptor inhibitor, have already been approved for cancer treatment. However, anti-angiogenic therapy has no specificity for target tissues; thus, angiogenesis inhibitors impede wound healing, causing bleeding and reopening of cuts. In this study, we investigated the possibility of genetic anti-angiogenic therapies that specifically target cancer cells using lentiviral vector-mediated transfection of the Cas9 gene, which is controlled by the promoter region of the growth factor cytokine, midkine. Midkine is a growth factor highly expressed in cancer cells, and its promoter region can be used to selectively regulate gene expression in cancer cells.

Methods: Two lentiviral vectors, one containing the human codon-optimized Cas9 (hCas9) gene and the other containing single guide RNA (sgRNA) sequences targeting VEGF-A, were used to infect human bladder cancer-derived cells.

Results: The gene expression level of hCas9 in bladder cancer cell lines was significantly higher than that in non-malignant cells, and VEGF-A disruption was observed only in bladder cancer cell lines.

Conclusions: These results suggest that placing cas9 under the control of the midkine promoter reduces its expression and activity in non-malignant cells. This approach is thus feasible as a safe anti-angiogenic therapy that does not affect non-target tissues and has few adverse side effects.

Aim: Makyoyokukanto (MKYK) is a traditional Japanese medicine used for relieving arthralgia, neuralgia, and myalgia. However, the effectiveness and safety of MKYK remains unclear. In this study, we assessed the effectiveness of MKYK in patients with painful afflictions.

Methods: One hundred and sixty-three patients (42 men and 121 women) with painful afflictions were recruited into the study. All participants were treated using non-invasive methods and administered MKYK. The effectiveness of MKYK was assessed following administration by evaluating the need for NSAIDs or other medication. In addition, adverse reactions were monitored.

Results: 85.9% of the patients were effectively treated with MKYK. Comorbidities were present in 52.8% of the study participants. The median duration of MKYK treatment was 14 days (2–364 days). The adverse event rate was 1.2%. The adverse events were insomnia caused by Ephedra herb and pseudoaldosteronism by Glycyrrhiza root. All symptoms improved after MKYK withdrawal.

Conclusion: The adverse event rate associated with MKYK use was low, and its onset was relatively rapid. This adverse event rate can be further reduced by focusing on the pharmacological action of Ephedra herb and Glycyrrhiza root. This study suggests that MKYK can be used more widely for painful afflictions.

Purpose: Dehydration is an important risk of SGLT2 inhibitors. Although dehydration may lead to thrombosis and embolism, especially cerebral infarction, this concern has not been clinically validated. As a result, cerebral infarction is considered a suspected risk of these inhibitors. To determine whether treatment with SGLT2 inhibitors lead to cardiovascular adverse events, spontaneous adverse event reports were retrieved from a database and assessed using two statistical approaches.

Methods: Two approaches were employed to evaluate the spontaneous reports from the Japanese Adverse Drug Event Report (JADER) database: (1) the traditional safety signal, proportional reporting ratios (PRRs), of cardiovascular adverse events related to treatment with SGLT2 inhibitors; and (2) the new safety signal, odds ratios (ORs), between dehydration (Preferred Term [PT]) and cardiovascular adverse events in SGLT2 inhibitor reports.

Results: A positive PRR (7.13) was found between cerebral infarction [PT] and treatment with SGLT2 inhibitors. However, cerebral infarction [PT] was not associated with dehydration [PT] (OR = 0.35) in the SGLT2 inhibitor reports. Such finding does not align with the concern that dehydration due to treatment with SGLT2 inhibitors may lead to cerebral infarction.

Conclusion: Cerebral infarction due to dehydration has been a concern for patients with diabetes treated with SGLT2 inhibitors. However, to contradict the concern, the relationship between SGLT2 inhibitors, dehydration, and cerebral infarction was not clear. It is believed that this study brings us closer to more informed drug selection assessing the risks and benefits of patient and that is, a personalized medicine approach.

The most perilous immediate response to Hymenoptera stings is a systemic allergic reaction known as anaphylaxis. Given that eppikajutsuto (EKJT) exhibits the capacity to mitigate inflammatory swelling while possessing heat^{Traditional Medicine module 1 (TM1)}-clearing and fluid^TM1-regulating properties, we used it to treat an anaphylactic reaction to a wasp sting. A 67-year-old woman was brought to the emergency department with anaphylaxis resulting from a paper wasp sting. As her blood pressure was 210/90 mmHg, EKJT was administered instead of adrenaline, and remarkable symptomatic improvement was observed. This case demonstrates that EKJT can alleviate symptoms associated with anaphylactic reactions to Hymenoptera stings.

Folate is an important coenzyme for DNA biosynthesis and for many metabolic processes. Folate deficiency causes macrocytic anemia, cardiovascular disease (CVD) and breast cancer. There are many kinds of folate supplements such as synthetic folic acid (FA) and L-5-methyltetrahydrofolate as well as from natural sources like Chlorella. 5, 10-methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism via one-carbon metabolism. MTHFR C677T polymorphism is related with autism, Alzheimer's disease, neural tube defects and CVD. We studied the effects of Chlorella pyrenoidosa on subjects of who had MTHFR C677T polymorphism. Seven outpatients were enrolled. Three were mutant homozygous genotype TT (TT), three were heterozygous genotype CT (CT) and one was CC type (CC). We conducted blood biochemical tests before and during supplementing with Chlorella pyrenoidosa for 3 months. There was a negative correlation (r = -0.43, p = 0.33) between folate and homocysteine before taking Chlorella pyrenoidosa. The TT group had a tendency of low folate concentration before this study (TT group 5.53 ng/mL, CT group 14.13 ng/mL) which increased after taking Chlorella pyrenoidosa (6.73 ng/mL). Two subjects showed an increase in serum albumin and iron levels. One case of hyperlipidemia (CT) showed a decrease of total cholesterol (305 mg/dL before, 256 mg/dL after). Blood sample analyses suggested that those with a baseline of low folate concentration showed a high serum homocysteine. High homocysteine has been reported to have a negative relationship with many health conditions. TT polymorphisms showed a tendency towards a low concentration of folate. This study showed the possibility of beneficial effects of Chlorella pyrenoidosa for folate metabolism and other nutritional benefits.