Selective delivery of imaging probes and therapeutics to the endoplasmic reticulum or Golgi apparatus: Current strategies and beyond.

To maximize therapeutic effects and minimize unwanted effects, the interest in drug targeting to the endoplasmic reticulum (ER) or Golgi apparatus (GA) has been recently growing because two organelles are distributing hubs of cellular building/signaling components (e.g., proteins, lipids, Ca2+) to other organelles and the plasma membrane. Their structural or functional damages induce organelle stress (i.e., ER or GA stress), and their aggravation is strongly related to diseases (e.g., cancers, liver diseases, brain diseases). Many efforts have been developed to image (patho)physiological functions (e.g., oxidative stress, protein/lipid-related processing) and characteristics (e.g., pH, temperature, biothiols, reactive oxygen species) in the target organelles and to deliver drugs for organelle disruption using organelle-targeting moieties. Therefore, this review will overview the structure, (patho)physiological functions/characteristics, and related diseases of the organelles of interest. Future direction on ER or GA targeting will be discussed by understanding current strategies and investigations on targeting, imaging/sensing, and therapeutic strategies.

Relationship between rheological properties, sensory perception, and overall acceptability of thickened liquids for dysphagia in young and old healthy individuals.

This study investigated the relationship between rheological properties, sensory perception, and overall acceptability in healthy young and old groups for dysphagia thickened liquids. Unflavored (UTL) and flavored (FTLP) thickened liquids were prepared using tap water or pomegranate juice at 10 different viscosity levels. The rheological properties were then evaluated via syringe flow test and line spread test (LST). When the apparent viscosity levels of UTL and FTLP were similar, the syringe test and LST results were also similar, indicating consistent flow behavior. Sensory perception evaluations showed that the young group better distinguished viscosity differences between stages compared to the old group. Regarding overall acceptability, the old group preferred samples with higher apparent viscosity than the young group. Principal component analysis and k-means cluster analysis were used to explore correlations between variables and classify thickened liquids into four groups. This can serve the foundation for standardized texture grades of dysphagia thickened liquids, considering rheological characteristics and sensory profiles.

Enhanced toxicity-free astaxanthin extraction from Haematococcus pluvialis via concurrent cell disruption and demulsification.

The extraction of astaxanthin from Haematococcus pluvialis involves the utilization of petroleum-derived organic solvents or supercritical CO2, beset by safety concerns, high costs, and environmental sustainability limitations. This study, in contrast, employed a method involving the adjustment of salt concentration, propylene glycol, and vegetable oil fraction to disrupt emulsion in aqueous cell lysates for facilitating the separation of astaxanthin. Under optimized conditions, an astaxanthin-containing oil with a content of 1.88% was obtained even with the use of wet biomass, and four rounds of consecutive extraction resulted in a cumulative recovery yield of 66.41%. This process produced astaxanthin-enriched soybean oil with 9.49 times improved antioxidant capacity that satisfies a requirement for health functional application. Omitting the solvent removal and drying processes, which consume tremendous energy, can reduce the production cost by 2.98 times compared to conventional methods. Consequently, this study suggests an effective technique for producing edible oil containing H. pluvialis-derived astaxanthin.

Increased Multiplexity in Optical Tissue Clearing-Based Three-Dimensional Immunofluorescence Microscopy of the Tumor Microenvironment by Light-Emitting Diode Photobleaching.

Optical tissue clearing and three-dimensional (3D) immunofluorescence (IF) microscopy is transforming imaging of the complex tumor microenvironment (TME). However, current 3D IF microscopy has restricted multiplexity; only 3 or 4 cellular and noncellular TME components can be localized in cleared tumor tissue. Here we report a light-emitting diode (LED) photobleaching method and its application for 3D multiplexed optical mapping of the TME. We built a high-power LED light irradiation device and temperature-controlled chamber for completely bleaching fluorescent signals throughout optically cleared tumor tissues without compromise of tissue and protein antigen integrity. With newly developed tissue mounting and selected region-tracking methods, we established a cyclic workflow involving IF staining, tissue clearing, 3D confocal microscopy, and LED photobleaching. By registering microscope channel images generated through 3 work cycles, we produced 8-plex image data from individual 400 µm-thick tumor macrosections that visualize various vascular, immune, and cancer cells in the same TME at tissue-wide and cellular levels in 3D. Our method was also validated for quantitative 3D spatial analysis of cellular remodeling in the TME after immunotherapy. These results demonstrate that our LED photobleaching system and its workflow offer a novel approach to increase the multiplexing power of 3D IF microscopy for studying tumor heterogeneity and response to therapy.

Comparison of microbial diversity and metabolites on household and commercial doenjang.

In this study, the microbial diversity, free amino acid (FAA), and biological activities of household doenjang (HDJ) from four different regions and commercial doenjang (CDJ) four manufacturers were analyzed. And volatile flavor compound (VFC) and isoflavone profiles were analyzed using gas chromatograph-mass spectrometer (GC-MS) and high performance liquid chromatography (HPLC), respectively. The major bacterial genus in 1HDJ and 2HDJ was Bacillus (97.5%), while in 3HDJ and 4HDJ, it was Enterobacter (47.5%) and Pseudomonas (80%), respectively. Tetragenococcus was the main bacterial genus of CDJ. The Zygosaccharomyces genus among yeast was comparatively high in all samples. In all samples, glutamic acid predominated among the FAAs, and the 3-methyl butanal, benzeneacetaldehyde, and diallyl disulphide were major VFCs. CDJ contained higher levels of isoflavone-glycoside and total phenolics. Except for 3HDJ and 4CDJ, the isoflavone-aglycone and total flavonoid contents were higher in HDJ. The correlation between bacterial genus and metabolited of doenjang showed that Tetragenococcus was closely related to glutamic acid, Bacillus was related to aglycones and ammonia, and Pseudomonas was highly related to isovaleric acid. While, correlation between yeast genus and metabolited of doenjang confirmed that Candida, Hanseniaspora, and Saccharomyces were related with furfural, benzeneacetaldehyde, and 3-methyl butanal, respectively. The results of this study can be utilized as basic data for the industrialization and development of doenjang.

Changes in walking practice and associated factors during the coronavirus disease 2019 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has induced many lifestyle changes, with reductions in healthy activities, including walking. The aim of this cross-sectional study was to identify strategies to maintain good health during a pandemic. Demographics, walking habits, health behaviors, health status, recognition of social capital, and changes in walking practice of 800 residents were evaluated using a structured questionnaire. Among the participants, 73.9%, 15.8%, and 10.4% reported no change, a decrease, and an increase in walking practice, respectively. Individuals in their 50 s and 60 s showed 6.388- and 5.054-times greater increases in walking, respectively, than did those aged 19-29 years. Walking increased more among high-income people than among low-income people. Additionally, walking practice increased in people participating in social gatherings, those with pets that needed walks, those with a COVID-19 history, those who considered walking as both a habitual and leisure activity, those with nearly no stress, and those satisfied with their safety, the natural environment, and public transportation; other health behaviors or conditions were not related to an increase in walking practice. To maintain good health during a pandemic, walking practice should be promoted in people in their 20 s and low-income groups. Moreover, people should be encouraged to attend meetings, including online interaction, and safe walking routes should be created within the community. Walking should be encouraged as a method of relieving stress, and the benefits of walking for recovery after an infectious disease should be emphasized. Furthermore, the direct effects of walking should be studied.

Report from an online workshop on family physician socialization: Reaffirmation using a hypothetical case.

This letter provides a report of our online workshop on the professional socialization of family physicians attended by family medicine residents and staff doctors in Japan. Participants engaged in small group discussions after reading hypothetical cases that threatened the identity of family physicians. Participants considered the importance of reaffirming and improving their strengths during discussions.

Electrocardiographic P terminal force in lead V1, its components, and the association with stroke and atrial fibrillation or flutter.

BACKGROUND: The electrocardiographic (ECG) marker P terminal force V1 (PTFV1) is generally perceived as a marker of left atrial pathology and has been associated with atrial fibrillation or flutter (AF). OBJECTIVE: The purpose of this study was to determine the association between PTFV1 components (duration and amplitude) and incident AF and stroke/transient ischemic attack (TIA). METHODS: The study included patients with an ECG recorded at the Copenhagen General Practitioners Laboratory in 2001 to 2011. PTFV1 ≥4 mV·ms was considered abnormal. Patients with abnormal PTFV1 were stratified into tertiles based on duration (PTDV1) and amplitude (PTAV1) values. Cox regressions adjusted for age, sex, and relevant comorbidities were used to investigate associations between abnormal PTFV1 components and AF and stroke/TIA. RESULTS: Of 267,636 patients, 5803 had AF and 18,176 had stroke/TIA (follow-up 6.5 years). Abnormal PTFV1 was present in 44,549 subjects (16.7%) and was associated with an increased risk of AF and stroke/TIA. Among patients with abnormal PTFV1, the highest tertile of PTDV1 (78-97 ms) was associated with the highest risk of AF (hazard ratio [HR] 1.37; 95% confidence interval [CI] 1.23-1.52) and highest risk of stroke/TIA (HR 1.13; 95% CI 1.05 -1.20). For PTAV1, the highest tertile (78-126 µV) conferred the highest risk of AF and stroke/TIA (HR 1.20; 95% CI 1.09-1.32; and HR 1.21; 95% CI 1.14-1.25, respectively). CONCLUSION: Abnormal PTFV1 was associated with an increased risk of AF and stroke/TIA. Increasing PTDV1 showed a dose-response relationship with the development of AF and stroke/TIA, whereas the association between PTAV1 and AF was less apparent.

Characterization of a conjugated polysuccinimide-carboplatin compound

Carboplatin, an advanced anticancer drug with excellent efficacy against ovarian cancer, was developed to alleviate the side effects that often occur with cisplatin and other platinum-based compounds. Our study reports the in vitro characteristics, viability, and activity of cells expressing the inducible nitric oxide synthase (iNOS) gene after carboplatin was conjugated with polysuccinimide (PSI) and administered in combination with other widely used anticancer drugs. PSI, which has promising properties as a drug delivery material, could provide a platform for prolonging carboplatin release, regulating its dosage, and improving its side effects. The iNOS gene has been shown to play an important role in both cancer cell survival and inhibition. Herein, we synthesized a PSI-carboplatin conjugate to create a modified anticancer agent and confirmed its successful conjugation. To ensure its solubility in water, we further modified the structure of the PSI-carboplatin conjugate with 2-aminoethanol groups. To validate its biological characteristics, the ovarian cancer cell line SKOV-3 and normal ovarian Chinese hamster ovary cells were treated with the PSI-carboplatin conjugate alone and in combination with paclitaxel and topotecan, both of which are used in conventional chemotherapy. Notably, PSI-carboplatin conjugation can be used to predict changes in the genes involved in cancer growth and inhibition. In conclusion, combination treatment with the newly synthesized polymer-carboplatin conjugate and paclitaxel displayed anticancer activity against ovarian cancer cells but was not toxic to normal ovarian cancer cells, resulting in the development of an effective candidate anticancer drug without severe side effects.

Diabetes Mellitus and Functional Food / 임상당뇨병

As the number of diabetes cases increases, prevention and treatment are more important. The food industry continues to research and develop safer blood sugar-lowering agents using natural products and anti-diabetic foods. Functional foods (FFs) are those that can be expected to provide specific health effects. Although patients do not recognize FFs as medicines, they perceive them to be healthier than regular foods. However, lack of control of food can lead to side effects such as worsening diabetes and increasing complications, in addition to economic losses due to excessive cost. Therefore, diabetes educators need to provide proper information to inform patients on studying ingredients before consuming FFs and to recognize problems of excessive consumption. It is assumed that FFs are consumed properly without abuse, and that nutrition therapy, exercise, and drug therapy are the basics of diabetics control.

A Critical Systematic Review for Inhaled Corticosteroids on Lung Cancer Incidence: Not Yet Concluded Story / 결핵및호흡기질환

Background@#To systematically review studies on inhaled corticosteroids (ICS) and lung cancer incidence in chronic airway disease patients. @*Methods@#We conducted electronic bibliographic searches on OVID-MEDLINE, EM- BASE, and the Cochrane Database before May 2020 to identify relevant studies. Detailed data on the study population, exposure, and outcome domains were reviewed. @*Results@#Of 4,058 screened publications, 13 eligible studies in adults with chronic obstructive pulmonary disease (COPD) or asthma evaluated lung cancer incidence after ICS exposure. Pooled hazard ratio and odds ratio for developing lung cancer in ICS exposure were 0.81 (95% confidence interval, 0.64 to 1.02; I2=95.7%) from 10 studies and 1.02 (95% confidence interval 0.50 to 2.07; I2=94.7%) from three studies. Meta-regression failed to explain the substantial heterogeneity of pooled estimates. COPD and asthma were variously defined without spirometry in 11 studies. Regarding exposure assessment, three and 10 studies regarded ICS exposure as a time-dependent and fixed variable, respectively. Some studies assessed ICS use for the entire study period, whereas others assessed ICS use for 6 months to 2 years within or before study entry. Smoking was adjusted in four studies, and only four studies introduced 1 to 2 latency years in their main or subgroup analysis. @*Conclusion@#Studies published to date on ICS and lung cancer incidence had heterogeneous study populations, exposures, and outcome assessments, limiting the generation of a pooled conclusion. The beneficial effect of ICS on lung cancer incidence has not yet been established, and understanding the heterogeneities will help future researchers to establish robust evidence on ICS and lung cancer incidence.

The role of discharge checklist in guideline-directed medical therapy for heart failure patients

Background/Aims@#Initiation of guideline-directed medical therapy (GDMT) during hospitalization is recommended for patients with heart failure (HF). However, GDMT is underutilized in real-world practice. This study evaluated the role of a discharge checklist on GDMT. @*Methods@#This was a single-center, observational study. The study included all patients hospitalized for HF between 2021 and 2022. The clinical data were retrieved from the electronic medical records and discharge checklist published by the Korean Society of Heart Failure. The adequacy of GDMT prescriptions was evaluated in three ways: the total number of GDMT drug classes and two types of adequacy scores. The primary endpoint was the incidence of all-cause mortality or rehospitalization due to HF within 2 months of discharge. @*Results@#Overall, the checklist was completed by 244 patients (checklist group) and was not completed in 171 patients (non-checklist group). The baseline characteristics were comparable between two groups. At discharge, a higher proportion of patients in the checklist group received GDMT than in the non-checklist group (67.6% vs. 50.9%, p = 0.001). The incidence of primary endpoint was lower in the checklist group compared to the non-checklist group (5.3% vs. 11.7%, p = 0.018). The use of the discharge checklist was associated with significantly lower risk of death and rehospitalization in the multivariable analysis (hazard ratio, 0.45; 95% confidence interval, 0.23–0.92; p = 0.028). @*Conclusions@#Discharge checklist usage is a simple but effective strategy for GDMT initiation during hospitalization. The discharge checklist was associated with better outcome in patients with HF.

Clinical outcomes of and risk factors for secondary infection in patients with severe COVID-19: a multicenter cohort study in South Korea

Background/Aims@#Secondary infection with influenza virus occurs in critically ill patients and is associated with substantial morbidity and mortality; however, there is limited information about it in patients with severe coronavirus disease 2019 (COVID-19). Thus, we investigated the clinical outcomes of and risk factors for secondary infections in patients with severe COVID-19. @*Methods@#This study included patients with severe COVID-19 who were admitted to seven hospitals in South Korea between February 2020 to February 2021. Multivariate logistic regression analyses were performed to assess factors associated with the risk of secondary infections. @*Results@#Of the 348 included patients, 104 (29.9%) had at least one infection. There was no statistically significant difference in the 28-day mortality (17.3% vs. 12.3%, p = 0.214), but in-hospital mortality was higher (29.8% vs. 15.2%, p = 0.002) in the infected group than in the non-infected group. The risk factors for secondary infection were a high frailty scale (odds ratio [OR], 1.314; 95% confidence interval [CI], 1.123 to 1.538; p = 0.001), steroid use (OR, 3.110; 95% CI, 1.164 to 8.309; p = 0.024), and the application of mechanical ventilation (OR, 4.653; 95% CI, 2.533 to 8.547; p < 0.001). @*Conclusions@#In-hospital mortality was more than doubled in patients with severe COVID-19 and secondary infections. A high frailty scale, the use of steroids and application of mechanical ventilation were risk factors for secondary infection.

Long-term cardiovascular events in hypertensive patients: full report of the Korean Hypertension Cohort

Background/Aims@#This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension. @*Methods@#The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension. @*Results@#The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events. @*Conclusions@#This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.

Neutral zone approach for rehabilitation in a patient who underwent mandibulotomy: A case report / 대한치과보철학회지

We present the case of a 65-year-old man with maxillary and mandibular complete dentures prepared using neutral zone technique after undergoing mandibulotomy due to tonsil cancer 10 years ago. The patient had a short edentulous period; hence, there was minimal absorption of the alveolar ridge and no abnormality in the motor function of the tongue. However, the retromolar pad was located inside the hamular notch, and the posterior alveolar ridge was relatively turned inward. If the artificial teeth would have been aligned conventionally, the functional space of the tongue would have been invaded, which would have moved the tongue posteriorly thereby reducing the stability of the denture. Therefore, applying the concept of the neutral zone can be a good reference point in such cases. The neutral zone was registered using tissue conditioner, and tooth alignment was performed by making a silicone putty index. The biggest advantage of using neutral zone concept is denture stability. In this case, the neutral zone technique was applied to obtain the lingual alignment limit of the posterior teeth to avoid invasion of the tongue space by the left posterior part of the mandible. Particularly, in case of a patient in which denture stability is difficult to obtain due to absorption of the alveolar ridge, it is believed that better results can be obtained using neutral zone technique.

Low body mass index is associated with poor treatment outcome following radiotherapy in esophageal squamous cell carcinoma

Purpose@#We aimed to determine whether patients with esophageal cancer with a low baseline body mass index (BMI) have a poor prognosis following radiotherapy (RT). @*Materials and Methods@#We retrospectively analyzed data from 50 patients with esophageal cancer to determine whether a low starting BMI (before RT) was associated with a poor outcome. All study participants were diagnosed with non-metastatic esophageal squamous cell carcinoma (SCC). @*Results@#The number of patients at each T stage were as follows: 7 (14%) patients at T1, 18 (36%) at T2, 19 (38%) at T3, and 6 (12%) at T4. Based on BMI, 7 (14%) patients were defined as underweight. A low BMI was common in patients with T3/T4 stage esophageal cancer (7/43, p = 0.01). Overall, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 26.3% and 69.2%, respectively. In univariate analysis, clinical factors associated with poor PFS included being underweight (BMI <18.5 kg/m2; p = 0.011) and a positive N status (p = 0.017). Univariate analysis also revealed that being underweight was associated with a decrease in OS (p = 0.003). However, being underweight was not an independent prognostic factor for PFS and OS. @*Conclusion@#Patients with esophageal SCC with a low starting BMI (BMI <18.5 kg/m2) are more prone to have a negative survival outcome following RT than patients who are considered to be normal weight or overweight. For this reason, it is important that clinicians pay more attention to BMI when treating patients with esophageal SCC.

A case report of successfully treated metachronous gastrointestinal stromal tumor and colon cancer / 고신대학교의과대학학술지

The diagnosis of gastrointestinal stromal tumor (GIST) has become relatively common in recent years, but little is known about its association with other malignancies. We present a rare case of successfully treated metachronous GIST and colon cancer with concurrent FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy and imatinib. A 63-year-old man presented with abdominal pain that had started 2 weeks ago, and endoscopic ultrasonography showed masses that were compatible with GIST on the duodenum. He underwent Whipple surgery. One year after the GIST diagnosis, two liver masses were found on abdominal computed tomography images taken for surveillance. A liver biopsy showed metastatic adenocarcinoma, not GIST. Colonoscopy was then performed to identify the primary site of the metastatic adenocarcinoma in the liver, and sigmoid colon cancer was found. He received 12 cycles of adjuvant FOLFOX concurrently with adjuvant imatinib. There were no serious adverse events of grade 3 or higher from either imatinib or chemotherapy. He has completed adjuvant imatinib and FOLFOX chemotherapy and there is no evidence of disease recurrence. When a synchronous or metachronous tumor is found in a GIST patient, the clinician should keep in mind the possibility of another primary tumor of different histopathology, as well as GIST recurrence.

Remote health monitoring services in nursing homes / 고신대학교의과대학학술지

Aged people are challenged by serious complications from chronic diseases, such as mood disorder, diabetes, heart disease, and infectious diseases, which are also the most common causes of death in older people. Therefore, elderly care facilities are more important than ever. The most common causes of death in elderly care facilities were reported to be diabetes, cardiovascular disease, and pneumonia. Recently, the coronavirus disease 2019 (COVID-19) pandemic have a great impact on blind spots of safety where aged people were isolated from society. Elderly care facilities were one of the blind spots in the midst of the pandemic, where major casualties were reported from COVID-19 complications because most people had one or two mortality risk factors, such as diabetes or cardiovascular disease. Therefore, medical governance of public health center and hospital, and elderly care facility is becoming important issue of priority. Thus, remote health monitoring service by the Internet of Medical Things (IoMT) sensors is more important than ever. Recently, technological breakthroughs have enabled healthcare professionals to have easy access to patients in medical blind spots through the use of IoT sensors. These sensors can detect medically urgent situations in a timely fashion and make medical decisions for aged people in elderly care facilities. Real-time electrocardiograms and blood sugar monitoring sensors are approved by the medical insurance service. Real-time monitoring services in medical blind spots, such as elderly care facilities, has been suggested. Heart rhythm monitoring could play a role in detecting early cardiovascular disease events and monitoring blood glucose levels in the management of chronic diseases, such as diabetes, in aged people in elderly care facilities. This review presents the potential usefulness of remote monitoring with IoMT sensors in medical blind spots and clinical suggestions for applications.

Clinical Implications of Expression of Endoglin and Survivin in Patients with Primary Cutaneous Angiosarcoma in an Asian Population / 대한피부과학회지

Background@#Targeted therapy and immunotherapy such as programmed death-1 (PD-1) targeting have been introduced for treating many types of cancers, including primary cutaneous angiosarcoma (CA). However, studies that examined other targeted molecules in CA are scarce. @*Objective@#We aim to declare the expression of endoglin and survivin in addition to PD-1 and assess the clinical correlation between the expression of these molecules and clinical variables, overall survival (OS), and progressionfree survival (PFS) in CA. @*Methods@#We identified 51 patients diagnosed with CA at Asan Medical Center over the last 14 years, based on the staining results of paraffin sections of tissue samples for endoglin, survivin, and PD-1 that were reviewed by two dermatologists. @*Results@#Statistical analysis for the correlation between results and clinical data of CA revealed that whereas 35 (63.6%) and 30 samples (54.5%) were positive for endoglin and survivin respectively, only nine samples were positive for PD-1 (16.4%). Co-expression of endoglin and survivin was detected in 24 lesions (p=0.013) and was significantly correlated to head, neck, face, and scalp (HNFS) lesions in CA (p=0.005, p=0.038, respectively). However, the expression of these target molecules did not correlate with the OS or PFS of CA. @*Conclusion@#Considering that HNFS type CA is associated with unfavorable clinical outcomes in similar populations, our findings can be helpful in matching patients with CA with effective targeted therapy.

Anti-Melanogenic Effect of Adiponectin on Co-Culture Models and Human Skin Tissues Ex Vivo / 대한피부과학회지

Background@#Adiponectin is an adipose-derived hormone that plays a role in various metabolic diseases. We previously demonstrated that adiponectin inhibits melanin synthesis through adenosine monophosphate-activated protein kinase (AMPK) activation in melanocytes. However, melanocytes can be affected by neighboring keratinocytes, and the effect of adiponectin on these functional units has not been investigated. @*Objective@#We investigated the effect of adiponectin on melanogenesis in co-cultured models of normal human melanocytes (NHMs), normal human keratinocytes (NHKs), and human dermal fibroblasts (HDFs), and the effect of adiponectin on melanin content in human skin tissues. @*Methods@#Quantitative real-time polymerase chain reaction (qPCR) was performed for tyrosinase and microphthalmia-associated transcription factor (MITF). The degree of phosphorylation of AMPK, cAMP response element binding protein (CREB), and AKT was evaluated by western blot assay, and Fontana-Masson staining was performed on cultured human skin tissues. @*Results@#Adiponectin decreased the melanin content in the co-culture models of NHMs with NHKs, NHMs with HDFs, and NHMs with both NHKs and HDFs. qPCR revealed that both tyrosinase and MITF were decreased after adiponectin treatment in the co-culture system. Following adiponectin treatment, AMPK was activated in all cell groups; however, the phosphorylation of CREB was decreased in HDFs and NHKs. The phosphorylation of AKT was decreased in only NHMs. In the experiment with human skin tissues cultured ex vivo, the densitometric analysis of Fontana-Masson staining revealed that adiponectin treatment reduced the melanin level of ultraviolet-irradiated human skin tissues. @*Conclusion@#Adiponectin inhibited melanogenesis in both co-culture models and human skin tissues ex vivo.