Zinc-deficient Group Research Articles

Zinc deficiency deteriorates ovarian follicle development and function by inhibiting mitochondrial function

Zinc (Zn) is a crucial trace element essential for human growth and development, particularly for reproductive health. Previous research has shown a decrease in serum zinc concentration with age and individuals with conditions such as polycystic ovary syndrome (PCOS) and diabetes mellitus. However, the specific effects of zinc deficiency on the female reproductive system, especially ovarian function, are not fully understood. In our study, we observed a significant reduction in the total number of follicles and mature follicles in the zinc deficiency group. This reduction correlated with decreased level of anti-Mullerian hormone (AMH) and abnormal gene expression affecting hormone secretion regulation. Furthermore, we found that zinc deficiency disrupted mitochondrial dynamics, leading to oxidative stress in the ovaries, which further inhibited autophagy and increased ovarian apoptosis. These changes ultimately resulted in the failure of germinal vesicle breakdown (GVBD) and reduced oocyte quality. Meanwhile, administration of zinc glycine effectively alleviated the oocyte meiotic arrest caused by dietary zinc deficiency. In conclusion, our findings demonstrated that dietary zinc deficiency can affect hormone secretion and follicle maturation by impairing mitochondrial function and autophagy.

Intestinal Barrier Impairment Induced by Gut Microbiome and Its Metabolites in School-Age Children with Zinc Deficiency.

Zinc deficiency affects the physical and intellectual development of school-age children, while studies on the effects on intestinal microbes and metabolites in school-age children have not been reported. School-age children were enrolled to conduct anthropometric measurements and serum zinc and serum inflammatory factors detection, and children were divided into a zinc deficiency group (ZD) and control group (CK) based on the results of serum zinc. Stool samples were collected to conduct metagenome, metabolome, and diversity analysis, and species composition analysis, functional annotation, and correlation analysis were conducted to further explore the function and composition of the gut flora and metabolites of children with zinc deficiency. Beta-diversity analysis revealed a significantly different gut microbial community composition between ZD and CK groups. For instance, the relative abundances of Phocaeicola vulgatus, Alistipes putredinis, Bacteroides uniformis, Phocaeicola sp000434735, and Coprococcus eutactus were more enriched in the ZD group, while probiotic bacteria Bifidobacterium kashiwanohense showed the reverse trend. The functional profile of intestinal flora was also under the influence of zinc deficiency, as reflected by higher levels of various glycoside hydrolases in the ZD group. In addition, saccharin, the pro-inflammatory metabolites, and taurocholic acid, the potential factor inducing intestinal leakage, were higher in the ZD group. In conclusion, zinc deficiency may disturb the gut microbiome community and metabolic function profile of school-age children, potentially affecting human health.

Efficacy of Normalising Serum Zinc Level for Patients with Olfactory Dysfunction and Zinc Deficiency

Plain Language SummaryThis study examined how zinc levels relate to problems with smelling, which is called olfactory dysfunction. We studied 42 participants who had trouble smelling due to infections, injuries, or unknown reasons and who also had low zinc levels in their blood. After the participants consumed a zinc supplement to treat their low zinc levels, we placed the participants either in the group for those who had their zinc levels go back to normal or in the group for those who remained zinc deficient. We tested the participants’ sense of smell in different ways, including using an olfactometer, a card with different scents, and questionnaires. The group with normal zinc levels did much better in all the smell tests; the zinc-deficient group only improved in 1 test, which was the questionnaire. These results suggest that if someone has trouble smelling and they also lack the appropriate level of zinc, it might be difficult for them to get better. However, if they can improve their zinc level and bring it to a normal level, their sense of smell could improve. In summary, this study demonstrated a connection between zinc levels and smelling ability, indicating that repairing zinc deficiency may aid in treating olfactory dysfunction.

A Short-Term Zinc-Deficient Diet Maintains Serum Calcium Concentrations through Ca Absorption-Related Gene Expression in Rats.

We investigated the effects of short-term dietary zinc deficiency on zinc and calcium metabolism. Four-week-old male Wistar rats were divided into two pair-fed groups for a 1-wk treatment: zinc-deficient group (ZD, 1 ppm); control group (PF, 30 ppm). The mRNA expression of zinc transporters, such as Slc39a (Zip) 4, Zip5, Zip10, and Slc30a (ZnT) 1, in various tissues (liver, kidney, and duodenum) quickly responded to dietary zinc deficiency. Although there was no significant difference in serum calcium concentrations between the PF and ZD groups, serum 1,25-dihydroxycholecalciferol (1,25(OH)2D3) was higher in the ZD group than in the PF group. Moreover, short-term zinc deficiency significantly increased mRNA expression of transient receptor potential (TRP) cation channel subfamily vanilloid (V) member 6, S100 calcium binding protein G (S100g), and ATPase plasma membrane Ca2+ transporting 1 (Atp2b1) in the duodenum. Furthermore, short-term zinc deficiency increased vitamin D receptor (VDR) and cytochrome P450 family 24 subfamily A member 1 (Cyp24a1) mRNA expression in the kidney. These findings suggested that short-term zinc deficiency maintains serum calcium concentrations through Ca absorption-related gene expression in the duodenum, and that short-term zinc deficiency induced the expression of Cyp24a1 in kidney in response to an increase in the serum 1,25(OH)2D3 level.

Effects of Dietary Zinc Deficiency and Supplementation on Prepubertal Rat Testes: Sulfhydryl and Antioxidant Status.

The study was designed to investigate the effects of dietary zinc deficiency and supplementation on antioxidant system viz. superoxide-dismutase, glutathione reductase, glutathione peroxidase, glutathione- S-transferase, catalase and sulfhydryls levels (GSH, TSH, NPSH and PBSH) in testes of Wistar rats. Pre-pubertal rats were divided into two groups with 6 sub-groups each viz. zinc control (ZC), pair fed (PF), zinc deficient (ZD), zinc control supplementation (ZCS), pair-fed supplementation (PFS) and zinc deficient supplementation (ZDS). Experiments were set for 2- and 4-weeks followed by 4weeks of zinc supplementation. The zinc deficient group animals exhibited significant decrease in gonado-somatic index (2- and 4- weeks), sulfhydryls levels, GSH, GPx, GR (2 and 4-weeks) and GST concentration (2-weeks). However, after zinc supplementation significant improvement in gonadosomatic index, SH, GSH, antioxidant enzyme levels (GR, GPx, and GST) in deficient groups has been observed. Zinc deficiency during pre-pubertal period affected growth and caused dysregulation of the glutathione antioxidant system. The significant alterations in the levels of antioxidant enzymes and non-enzymatic antioxidant system (GSH and SH) in zinc deficient groups could be due to alleviated generation of free radicals, causative factor for increased oxidative stress which may lead to infertility as oxidative stress is a common pathology seen during infertility. Altered antioxidant system and sulfhydryls levels in testes due to dietary zinc deficiency reflect the significance of optimum zinc for maintaining homeostatic balance in gonadal physiology. Supplementing zinc for 4weeks could reduce the redox imbalance which may help in alleviating oxidative stress induced alterations in testes.

Association between the serum zinc level and nutritional status represented by the geriatric nutritional Rrisk index.

Although it is widely known that patients with chronic kidney disease (CKD) can develop zinc deficiency, in our previous analysis, the estimated glomerular filtration rate (eGFR) was not independently associated with the serum zinc level. Thus, a post hoc analysis was conducted to investigate the involvement of nutritional status. A total of 655 subjects not on dialysis (402 males; mean age, 57 ± 18years) who underwent serum zinc level measurements at Jikei University Hospital between April 2018 and March 2019 were selected using the Standardized Structured Medical Information eXchange2 (SS-MIX2) system. In addition, anthropometric data and the Geriatric Nutritional Risk Index (GNRI) representing nutritional status were obtained, and the relationship between the serum zinc level and nutritional status was investigated by multiple regression analysis. The serum albumin level and the GNRI were lower in the zinc-deficiency group, and both were positively associated with the serum zinc level (rho = 0.44, P < 0.01 and rho = 0.44, P < 0.01, respectively). On multiple regression analysis, the GNRI (t = 3.09, P < 0.01) and serum albumin level (t = 4.75, P < 0.01) were independently associated with the serum zinc level. Although a higher eGFR was associated with a higher serum zinc level, this association disappeared on multivariate analysis. In this post hoc analysis, the GNRI, as well as the serum albumin level, were correlated with the serum zinc level, indicating that nutritional status is an important determinant of the zinc level. Further investigations are needed to clarify the effects of nutritional status and kidney function on zinc deficiency.

The influence of zinc on apoptosis and cell proliferation in palatal shelves during the fusion phase in mice and identification of a special protein family based on gene expression in cleft palate

Objective: To investigate the effect of the trace element zinc (Zn) on apoptosis and cell proliferation in palate shelvesduring the fusion phase, and to screen candidate genes of the Zn-finger special protein (Sp) family that were differentially expressed between the cleft palate and the normal palate to explore the mechanism of Zn in the development of cleft palate. Methods: Zn-rich, normal-Zn, low-Zn, and Zn-deficient diets were fed to female mice and, for the resultant fetuses, paraffin slices of their heads were made at embryonicdays 14.5 and 16.5. Using terminaldeoxynucleotidyltransferase-mediated dUTP nick-end labeling, the number of apoptotic cells in the palatal shelves was counted, and cell proliferation activity was detected using proliferating cell nuclear antigen staining. Total RNA from the palatal shelves of fetal mice was extracted from the Zn-rich diet, normal Zn-diet, and Zn-deficient-diet groups. We used microarray analysis to examine the expression of genes to identify intergroup differential gene expression and polymerase chain reaction tests to validate the results. Results: At ED14.5, the incidence of cleft palate in the regular zinc group, zinc rich group, low zinc group, and zinc deficient group was 8% (3/36), 2% (1/39), 29% (12/41), and 39% (15/38), respectively. The HE staining results at ED14.5 showed that both the left and right palatal processes in the zinc group had been lifted up and were in contact and connected with each other. In the zinc deficiency group, the left and right palatine processes remained vertically downwards on both sides of the tongue, ultimately forming cleft palate; In the low zinc group, the left and right palatine processes were raised but not in contact, ultimately resulting in cleft palate. There is no significant difference between the zinc rich group and the regular zinc group. At ED14.5, the positive rates of proliferative cells in the palatal process of fetal mice in the regular zinc group (80.29% ± 7.39%) and the zinc rich group (87.69% ± 6.62%) were significantly higher than those in the zinc deficient group (56.05% ± 16.13%) and the low zinc group (56.22% ± 9.61%) (t=4.32, P<0.05). The apoptosis index of fetal rat palatal process cells in the zinc deficient group (38.80% ± 3.10%) and the low zinc group (28.80% ± 6.19%) were significantly higher than those in the regular zinc group (16.80% ± 1.82%) (t=19.35, P<0.001; t=5.81, P<0.001). There were 663 differentially expressed genes in the zinc rich group and the zinc deficient group, with 513 up-regulated genes and 150 down-regulated genes, among which Sp5 was found to be located. The real time PCR results showed that compared with the regular zinc group (2.22 ± 0.36), the expression level of Sp5mRNA in the palatal process tissue of the zinc deficient group (1.23 ± 0.38) significantly increased (P<0.05), while the zinc rich group (3.68 ± 0.90) significantly decreased (P<0.05). Conclusions: Trace element Zn content was found to be closely related to the occurrence of cleft palate in mice offspring, with a lack of Zn leading to cleft palate.

Marginal Maternal Zinc Deficiency Produces Liver Damage and Altered Zinc Transporter Expression in Offspring Male Rats.

The aim of this study was to investigate how zinc deficiency and supplementation affect liver markers including autotaxin, kallistatin, endocan, and zinc carrier proteins ZIP14 and ZnT9 in rats exposed to maternal zinc deficiency. Additionally, the study aimed to assess liver tissue damage through histological examination. A total of forty male pups were included in the research, with thirty originating from mothers who were given a zinc-deficient diet (Groups 1, 2, and 3), and the remaining ten born to mothers fed a standard diet (Group 4). Subsequently, Group 1 was subjected to a zinc-deficient diet, Group 2 received a standard diet, Group 3 received zinc supplementation, and Group 4 served as the control group without any supplementation. Upon completion of the experimental phases of the study, all animals were sacrificed under general anesthesia, and samples of liver tissue were obtained. The levels of autotaxin, kallistatin, endocan, ZIP 14, and ZnT9 in these liver tissue samples were determined using the ELISA technique. In addition, histological examination was performed to evaluate tissue damage in the liver samples. In the group experiencing zinc deficiency, both endocan and autotaxin levels increased compared to the control group. With zinc supplementation, the levels of endocan and autotaxin returned to the values observed in the control group. Similarly, the suppressed levels of kallistatin, ZIP14, and ZnT9 observed in the zinc deficiency group were reversed with zinc supplementation. Likewise, the reduced levels of kallistatin, ZIP14, and ZnT9 seen in the zinc deficiency group were rectified with zinc supplementation. Moreover, the application of zinc partially ameliorated the heightened liver tissue damage triggered by zinc deficiency. This study is the pioneering one to demonstrate that liver tissue dysfunction induced by a marginal zinc-deficient diet in rats with marginal maternal zinc deficiency can be alleviated through zinc supplementation.

Zinc deficiency effect on clinical features of Coronavirus Disease 2019 patients: A scoping review

COVID-19 was declared a pandemic in March 2020. Various therapeutic guidelines have been established for treating COVID-19, such as anti-inflammatory, antiviral therapies, and zinc supplementation. Zinc deficiency is thought to worsen the condition of patients with COVID-19 infection. However, the effect of zinc deficiency on COVID-19 patients has not been widely reported. In this scoping review, we aim to explore the impact of zinc deficiency on the clinical features of COVID-19 patients. A comprehensive search was conducted across the databases, including PubMed, ScienceDirect, Springer Link, ProQuest, and Google Scholar, using the keywords “Zinc” AND “(COVID-19 or SARS-CoV-2)”. A total of 2,458 articles published between 2019 and 2020 were screened following the PRISMA guidelines and subjected to critical appraisal. Three articles were included, focusing on the effect of zinc deficiency on the clinical features of COVID-19 patients. As of 2022, two articles reported worsening symptoms, one described an increased hospitalization duration, and one reported worsening treatment outcomes in the zinc deficiency group. This review concludes that zinc deficiency worsens symptoms, increases the duration of hospitalization, and leads to worse outcomes in COVID-19 patients.

Dietary Zinc Status in Offspring of Pregnant Rats Fed on a Zinc-Deficient Diet Is Associated with Serum Albumin, Ast, and Alt Levels

Objective: This study was carried out to investigate whether dietary zinc status is associated with serum albumin, AST and ALT levels in male offspring of mother rats fed a zinc deficient diet. Methods: The study was carried out on male offspring (Groups 1, 2, 3) born to rats fed a zinc deficient diet and on male offspring (Group 4) born to mothers fed a standard diet. Group 1: Zinc deficient, Group 2; standard rat chow, Group 3: Zinc supplemented diet. Animals of group 4 were used as control group. After the completion of the experimental stages of the study, albumin, AST, ALT, free and total bilirubin levels in serum samples taken from animals were determined by spectrophotometric method. Results: Dietary zinc deficiency (group 1) significantly decreased serum albumin values (p&lt;0.004). Animals in both the zinc deficient (Group 1) group and the Group 2 animals born to mothers fed a zinc deficient diet and fed standard rat chow had the highest AST and ALT levels (p&lt;0.001). Conclusion: The present study is the first to show that dietary zinc status can directly affect liver function in rats born to zinc deficient mothers by causing changes in serum albumin, AST and ALT levels.

Zinc Deficiency Causes Oxidative Damage to Proteins, Lipids and DNA in Rat Testes

To investigate the effects of zinc deficiency on oxidative damage to testes proteins, lipids and DNA, weanling male rats were allowed free access to low (0.5 µg Zn/g) or adequate (25 µg Zn/g) zinc diets for 14 d. A third group was restricted intake of the adequate Zn diet to the amount consumed by the low Zn diet-fed group. Compared with ad libitum-fed controls, testes from rats fed the low zinc diet had lower glutamine synthetase activity, lower Fe2+-stimulated 2-thiobarbituric acid-reactive substances (TBARS) production, higher protein carbonyl concentrations (P < 0.05), and higher 8-oxo-2′-deoxyguanosine levels (P = 0.06). Glutamine synthetase activity in testes of the food-restricted controls was between the values for the ad libitum controls and zinc-deficient animals. Protein carbonyls were higher in the restricted controls compared with the ad libitum controls, whereas stimulated TBARS production was lower (P < 0.05). Levels of 8-oxo-2′-deoxyguanosine were lower in testes DNA of the restricted controls than in the zinc-deficient group (P < 0.05). Testes iron concentrations were higher in the zinc-deficient and restricted control rats than in ad libitum controls (P < 0.05). The oxidative damage observed may have occurred as a consequence of increased reactive oxygen species generation secondary to tissue iron accumulation and/or reductions in zinc-dependent antioxidant processes.

Relationship between the severity of olfactory dysfunction and serum zinc levels.

Although the association between zinc deficiency and olfactory dysfunction is inconclusive, zinc deficiency causes apoptosis of the olfactory ensheathing cells which is involved in olfactory nerve turnover and axon regeneration, thereby suggesting a possible relationship. We investigated the relationship between serum zinc levels and olfactory function in patients with olfactory dysfunction. Ninety patients who had been diagnosed with post-infectious, posttraumatic, drug-induced, neurological and idiopathic olfactory dysfunction were included. Patients were divided into zinc normal group and zinc deficiency groups according to three reference values for serum zinc levels (60, 65, 70µg/dL). The results of olfactory tests and patient backgrounds were used to compare the differences between the two groups. There were significantly worse detection and recognition thresholds in the T&T olfactometer and Open Essence (odor identification test) results in the zinc deficiency group (< 60µg/dL). In addition, significant correlations between olfactory tests (detection/recognition thresholds in the T&T olfactometer and Open Essence results) and serum zinc levels < 65µg/dL were observed. The zinc deficiency group < 70µg/dL with idiopathic olfactory dysfunction had significantly worse olfactory tests (detection/recognition thresholds in the T&T olfactometer and Open Essence). In addition, there was a significant correlation between the detection/recognition thresholds in the T&T olfactometer and serum zinc levels in idiopathic olfactory dysfunction. Our findings suggest that zinc deficiency may exacerbate the severity of olfactory dysfunction. Furthermore, idiopathic olfactory dysfunction may be partly caused by zinc deficiency.

Association between zinc deficiency and aorta stiffness in non-diabetic hemodialysis patients.

Zinc deficiency (Zn < 60 μg/dL) is known to play an important role for vascular calcification. However, little data is available regarding the association between zinc deficiency and aorta stiffness in dialysis patients. Thus, we studied the relationship between zinc deficiency and aorta stiffness in non-diabetic hemodialysis (HD) patients. Of 150 patients receiving maintenance HD at our hospital, we included 79 non-diabetic HD patients (age: 70±11 years, 49 men) after excluding 71 diabetic HD patients. Zinc deficiency was defined as Zn <60 μg/dL during pre-HD blood sampling. The association between zinc deficiency and aorta stiffness was analyzed. Aorta stiffness was evaluated as brachial-ankle pulse wave velocity (baPWV). Other surrogate markers for cardiovascular complications were also measured. The zinc deficiency group (ZD group) included 45 patients (57.0%). Compared to the zinc non-deficiency group (ZND group), patients with ZD group were significantly older, higher levels of CRP and hypoalbuminemia. Moreover, they had significantly higher levels of baPWV, and lower levels of ankle-brachial pressure index (ABI) (p<0.05). After adjusting for hypoalbuminemia, and CRP, multivariate analysis showed that age and zinc level were independent predictors of baPWV. The study suggested that zinc deficiency may be an independent risk factor for aorta stiffness, even after adjusting for malnutrition and inflammation.

Effects of zinc deficiency on the regeneration of olfactory epithelium in mice.

The olfactory epithelium can regenerate after damage; however, the regeneration process is affected by various factors, such as viral infections, head trauma, and medications. Zinc is an essential trace element that has important roles in organ development, growth, and maturation. Zinc also helps regulate neurotransmission in the brain; nevertheless, its relationship with olfactory epithelium regeneration remains unclear. Therefore, we used a severe zinc deficiency mouse model to investigate the effects of zinc deficiency on olfactory epithelium regeneration. Male wild-type C57BL/6 mice were divided into zinc-deficient and control diet groups at the age of 4 weeks, and methimazole was administered at the age of 8 weeks to induce severe olfactory epithelium damage. We evaluated the olfactory epithelium before and 7, 14, and 28 d after methimazole administration by histologically analyzing paraffin sections. RNA sequencing was also performed at the age of 8 weeks before methimazole administration to examine changes in gene expression caused by zinc deficiency. In the zinc-deficient group, the regenerated olfactory epithelium thickness was decreased at all time points, and the numbers of Ki-67-positive, GAP43-positive, and olfactory marker protein-positive cells (i.e., proliferating cells, immature olfactory neurons, and mature olfactory neurons, respectively) failed to increase at some time points. Additionally, RNA sequencing revealed several changes in gene expression, such as a decrease in the expression of extracellular matrix-related genes and an increase in that of inflammatory response-related genes, in the zinc-deficient group. Therefore, zinc deficiency delays olfactory epithelium regeneration after damage in mice.

Zinc Deficiency: The Association with Vitamin B12 in People of Different Ages

Background: Zinc and vitamin B12 are the foremost important micronutrients. About a quarter of Iranian households have a zinc deficiency. Objectives: Considering the importance of these micronutrients, this study aimed to investigate the association between zinc deficiency and vitamin B12 in people of different ages who had their blood tested in the Pasteur laboratory in Ahvaz. Methods: In this cross-sectional study, serum levels of zinc and vitamin B12 were measured using atomic absorption spectrophotometry and electro-chemiluminescence, respectively. Then, samples were divided into normal and zinc-deficient groups based on serum zinc levels. Serum vitamin B12 levels were also compared between two defined groups. The correlation between age and both zinc and vitamin B12 were determined through statistical tests. Results: In 60.5% of samples, serum zinc was lower than in the normal group. However, the two groups had no statistically significant difference in zinc levels (P = 0.085). Findings showed that with increasing one year of age, serum zinc level decreases by 0.13 units, and serum level of vitamin B12 increases by 0.19 units. Although the serum level of vitamin B12 in the group with normal zinc levels was higher than in the zinc-deficient group, this difference was not statistically significant (P = 0.743). Conclusions: Zinc and Vitamin B12 serum levels can have a clinically positive correlation, and zinc deficiency might be effective in manipulating vitamin B12 status in the body.

Alteration in Gut Microbiota Associated with Zinc Deficiency in School-Age Children.

Zinc deficiency could lead to a dynamic variation in gut microbial composition and function in animals. However, how zinc deficiency affects the gut microbiome in school-age children remains unclear. The purpose of this study was to profile the dynamic shifts in the gut microbiome of school-age children with zinc deficiency, and to determine whether such shifts are associated with dietary intake. A dietary survey, anthropometric measurements, and serum tests were performed on 177 school-age children, and 67 children were selected to explore the gut microbial community using amplicon sequencing. School-age children suffered from poor dietary diversity and insufficient food and nutrient intake, and 32% of them were zinc deficient. The inflammatory cytokines significantly increased in the zinc deficiency (ZD) group compared to that in the control (CK) group (p < 0.05). There was no difference in beta diversity, while the Shannon index was much higher in the ZD group (p < 0.05). At the genus level, Coprobacter, Acetivibrio, Paraprevotella, and Clostridium_XI were more abundant in the ZD group (p < 0.05). A functional predictive analysis showed that the metabolism of xenobiotics by cytochrome P450 was significantly depleted in the ZD group (p < 0.05). In conclusion, gut microbial diversity was affected by zinc deficiency with some specific bacteria highlighted in the ZD group, which may be used as biomarkers for further clinical diagnosis of zinc deficiency.

Zinc Deficiency Blunts the Effectiveness of Antidepressants in the Olfactory Bulbectomy Model of Depression in Rats.

Currently used antidepressants do not always provide the desired results, and many patients suffer from treatment-resistant depression. Clinical studies suggest that zinc deficiency (ZnD) may be an important risk factor for depression and might blunt the effect of antidepressants. This study aimed to examine whether ZnD might blunt the effectiveness of antidepressants in the olfactory bulbectomy model (OB) of depression in rats. For this purpose, rats were subjected to the OB model, fed a zinc-deficient diet (3 mg Zn/kg) for 3 weeks, and finally treated with escitalopram (Esc), venlafaxine (Ven) 10 mg/kg, i.p., or combined Esc/Ven (1 mg/kg, i.p.) with zinc (5 mg/kg) for another 3 weeks. Open field (OFT), forced swim (FST), and sucrose intake (SIT) tests were used to evaluate depressive-like behavioral changes. In addition, serum, intracellular, and synaptic Zn concentrations and the level of zinc transporter (ZnT) proteins were analyzed. The OB + ZnD model induced hyperactivity in rats in the OFT, increased immobility time in the FST, and anhedonia in the SIT. Chronic treatment with Esc reduced immobility time in the FST in the OB + ZnD model. Esc/Ven +Zn increased sucrose intake in rats from the OB + ZnD group. The OB + ZnD decreased serum zinc levels and intracellular and synaptic Zn concentration in the prefrontal cortex (PFC) and cerebellum. These changes were normalized by chronic administration of Esc/Ven +Zn. Moreover, OB + ZnD decreased levels of the ZnT1 protein in the PFC and Hp and ZnT3 in Hp. Chronic administration of antidepressants did not alter the levels of ZnT proteins. The OB + ZnD model induces more depressive-like effects than either model alone. Our results show that ZnD may induce drug resistance in rats. Normalizing serum or brain zinc concentration is insufficient to reverse behavioral abnormalities caused by the OB + ZnD model. However, zinc supplementation might improve the effectiveness of antidepressants in reversing particular depression symptoms.

The Relationship Between Zinc Deficiency and Hepatocellular Carcinoma Associated with Hepatitis B Liver Cirrhosis: A 10-year Follow-up Study.

Our aim is to evaluate the serum zinc levels in Hepatitis B liver cirrhosis patients and clarify the relationship between the serum zinc levels and the development of hepatocellular carcinoma (HCC). From January 2009 to December 2019, 295 included patients diagnosed with Hepatitis B liver cirrhosis received nucleos(t)ide analogues (NUCs) therapy at China-Japan Union Hospital of Jilin University. Their comprehensive medical records were retrospectively analyzed, and to analyze the relationship between hypozincemia and hepatitis B-related HCC. Twenty-eight of 295 patients (9.49%) developed HCC during an observation period of the median follow-up time was 42 months. Compared with the non-zinc deficiency group, the zinc deficiency group is older, has a higher proportion of hepatic encephalopathy, higher levels of aspartate aminotransferase(AST), international normalized ratio(INR) and TB, and lower levels of cholinesterase (CHE), creatinine, and platelet counts (P< 0.05). Multivariate analysis showed that zine (HR=0.854, 95%CI 0.725-1.007; P=0.061), zinc is not significant for reducing the incidence of HCC, as liver disease progresses, the proportion of zinc deficiency is getting higher and higher, Child-Pugh C. The proportion of grade zinc deficiency accounted for 64.86%. Child-Pugh grade C was more than Child-Pugh grade B and A, p<0.001. Zinc deficiency is associated with hepatic encephalopathy, and other complications related to hepatitis B and liver cirrhosis. But the relationship with hepatocellular carcinoma still needs further study.

Clinical Significance of Serum Zinc Levels on the Development of Sarcopenia in Cirrhotic Patients.

Sarcopenia increases the mortality in patients with cirrhosis. Approximately 60% of zinc is accumulated in skeletal muscle. We aimed to determine the role of subclinical zinc deficiency on sarcopenia development in patients with cirrhosis. We enrolled 151 patients with cirrhosis and divided them into the group with normal serum zinc levels (Group N: 80-130 μg/dl; n=38) and group with subclinical zinc deficiency (Group D: <80 μg/dl; n=113). The risk factors for sarcopenia were then investigated. Group D had more sarcopenia cases than Group N (31.0% vs. 13.2%). In group D, HGS exhibited a weakly positive but significant correlation with serum zinc levels (R=0.287, p=0.00212), serum zinc levels negatively correlated with both ammonia and myostatin levels (R=-0.254, p=0.0078; R=-0.33, p<0.01), and low zinc levels were independently associated with sarcopenia development. Patients with cirrhosis showing subclinical zinc deficiency have a significantly higher risk of developing sarcopenia.

Dietary zinc deficiency disrupts skeletal muscle proteostasis and mitochondrial biology in rats

ObjectivesZinc deficiency is related to reduced growth, mass, and work capacity of skeletal muscle. However, the underlying mechanisms in connection with skeletal muscle proteostasis and mitochondrial biology are not clear. The aim of this study was to investigate the consequences of dietary zinc deficiency on skeletal muscle proteostasis and mitochondrial biology in growing rats. MethodsThree-wk-old male Wistar/Kyoto weanling rats were fed either a zinc-deficient diet (<1 mg/kg; ad libitum) or a control diet pair-fed with zinc-deficient group (47.5 mg/kg) for a 7-wk period. Skeletal (gastrocnemius) muscle myofiber cross-sectional area was measured on hematoxylin and eosin-stained sections. Real-time quantitative reverse transcription polymerase chain reaction and immunoblotting were performed to study the target gene and protein expression, respectively. The chymotrypsin-like proteasomal activity was analyzed by fluorescence method. ResultsResults showed a decreased mean muscle fiber cross-sectional area and increased apoptosis in the muscle of zinc-deficient rats. Activation of the ubiquitin-proteasome system as indicated by increased levels of the E1 enzyme, MuRF1 (muscle-specific E3 ligase; muscle atrophy marker) and proteasomal activity was observed in the zinc-deficient rats. Declined autophagy (Beclin1, ATG5, and LC3), and increased endoplasmic reticulum stress markers were observed. Zinc deficiency also affected mitochondrial biology including fission, fusion, transcription, and oxidative phosphorylation components. ConclusionZinc deficiency disturbed the skeletal muscle proteostasis, and mitochondrial biology, causing decreased cell size and increased cell death.