1.The Clinical Utility of Biomarkers in Diagnosing Major Depressive Disorder in Adults: A Systematic Review of Literature From 2013 to 2023
Shi-han ANG ; Roger C. HO ; Roger S. MCINTYRE ; Zhisong ZHANG ; Soon-kiat CHANG ; Kayla M. TEOPIZ ; Cyrus SH HO
Psychiatry Investigation 2025;22(4):341-356
Objective:
The variety and efficacy of biomarkers available that may be used objectively to diagnose major depressive disorder (MDD) in adults are unclear. This systematic review aims to identify and evaluate the variety of objective markers used to diagnose MDD in adults.
Methods:
The search strategy was applied via PubMed and PsycINFO over the past 10 years (2013–2023) to capture the latest available evidence supporting the use of biomarkers to diagnose MDD. Data was reported through narrative synthesis.
Results:
Forty-two studies were included in the review. Findings were synthesised based on the following measures: blood, neuroimagingeurophysiology, urine, dermatological, auditory, vocal, cerebrospinal fluid and combinatory—and evaluated based on its sensitivity/specificity and area under the curve values. The best predictors of blood (MYT1 gene), neuroimagingeurophysiological (5-HT1A auto-receptor binding in the dorsal and median raphe), urinary (combined albumin, AMBP, HSPB, APOA1), cerebrospinal fluid-based (neuron specific enolase, microRNA) biomarkers were found to be closely linked to the pathophysiology of MDD.
Conclusion
A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.
2.Development of Zinc-Containing Chitosan/Gelatin Coatings with Immunomodulatory Effect for Soft Tissue Sealing around Dental Implants
Jing HAN ; Jorine G. F. SANDERS ; Lea ANDRÉE ; Bart A. J. A. van OIRSCHOT ; Adelina S. PLACHOKOVA ; Jeroen J. J. P. van den BEUCKEN ; Sander C. G. LEEUWENBURGH ; Fang YANG
Tissue Engineering and Regenerative Medicine 2025;22(1):57-75
BACKGROUND:
Soft tissue integration (STI) around dental implant abutments is a prerequisite to prevent bacterial invasion and achieve successful dental implant rehabilitation. However, peri-implant STI is a major challenge after dental abutment placement due to alterations in the immune microenvironment upon surgical dental implant installation.
METHODS:
Based on known immunomodulatory effects of zinc, we herein deposited zinc/chitosan/gelatin (Zn/CS/Gel) coatings onto titanium substrates to study their effect on macrophages. First, we exposed macrophages to cell culture media containing different zinc ion (Zn2+) concentrations. Next, we explored the immunomodulatory effect of Zn/CS/Gel coatings prepared via facile electrophoretic deposition (EPD).
RESULTS:
We found that Zn2+ effectively altered the secretome by reducing the secretion of pro-inflammatory and enhancing pro-regenerative cytokine secretion, particularly at a Zn2+ supplementation of approximately 37.5 μM. Zn/CS/Gel coatings released Zn2+ in a concentration range which effectively stimulated pro-regenerative macrophage polarization as demonstrated by M2 macrophage polarization. Additionally, the impact of these Zn2+-exposed macrophages on gingival fibroblasts incubated in conditioned medium showed stimulated adhesion, proliferation, and collagen secretion.
CONCLUSION
Our promising results suggest that controlled release of Zn2+ from Zn/CS/Gel coatings could be applied to immunomodulate peri-implant STI, and to enhance dental implant survival.
3.The Clinical Utility of Biomarkers in Diagnosing Major Depressive Disorder in Adults: A Systematic Review of Literature From 2013 to 2023
Shi-han ANG ; Roger C. HO ; Roger S. MCINTYRE ; Zhisong ZHANG ; Soon-kiat CHANG ; Kayla M. TEOPIZ ; Cyrus SH HO
Psychiatry Investigation 2025;22(4):341-356
Objective:
The variety and efficacy of biomarkers available that may be used objectively to diagnose major depressive disorder (MDD) in adults are unclear. This systematic review aims to identify and evaluate the variety of objective markers used to diagnose MDD in adults.
Methods:
The search strategy was applied via PubMed and PsycINFO over the past 10 years (2013–2023) to capture the latest available evidence supporting the use of biomarkers to diagnose MDD. Data was reported through narrative synthesis.
Results:
Forty-two studies were included in the review. Findings were synthesised based on the following measures: blood, neuroimagingeurophysiology, urine, dermatological, auditory, vocal, cerebrospinal fluid and combinatory—and evaluated based on its sensitivity/specificity and area under the curve values. The best predictors of blood (MYT1 gene), neuroimagingeurophysiological (5-HT1A auto-receptor binding in the dorsal and median raphe), urinary (combined albumin, AMBP, HSPB, APOA1), cerebrospinal fluid-based (neuron specific enolase, microRNA) biomarkers were found to be closely linked to the pathophysiology of MDD.
Conclusion
A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.
4.Development of Zinc-Containing Chitosan/Gelatin Coatings with Immunomodulatory Effect for Soft Tissue Sealing around Dental Implants
Jing HAN ; Jorine G. F. SANDERS ; Lea ANDRÉE ; Bart A. J. A. van OIRSCHOT ; Adelina S. PLACHOKOVA ; Jeroen J. J. P. van den BEUCKEN ; Sander C. G. LEEUWENBURGH ; Fang YANG
Tissue Engineering and Regenerative Medicine 2025;22(1):57-75
BACKGROUND:
Soft tissue integration (STI) around dental implant abutments is a prerequisite to prevent bacterial invasion and achieve successful dental implant rehabilitation. However, peri-implant STI is a major challenge after dental abutment placement due to alterations in the immune microenvironment upon surgical dental implant installation.
METHODS:
Based on known immunomodulatory effects of zinc, we herein deposited zinc/chitosan/gelatin (Zn/CS/Gel) coatings onto titanium substrates to study their effect on macrophages. First, we exposed macrophages to cell culture media containing different zinc ion (Zn2+) concentrations. Next, we explored the immunomodulatory effect of Zn/CS/Gel coatings prepared via facile electrophoretic deposition (EPD).
RESULTS:
We found that Zn2+ effectively altered the secretome by reducing the secretion of pro-inflammatory and enhancing pro-regenerative cytokine secretion, particularly at a Zn2+ supplementation of approximately 37.5 μM. Zn/CS/Gel coatings released Zn2+ in a concentration range which effectively stimulated pro-regenerative macrophage polarization as demonstrated by M2 macrophage polarization. Additionally, the impact of these Zn2+-exposed macrophages on gingival fibroblasts incubated in conditioned medium showed stimulated adhesion, proliferation, and collagen secretion.
CONCLUSION
Our promising results suggest that controlled release of Zn2+ from Zn/CS/Gel coatings could be applied to immunomodulate peri-implant STI, and to enhance dental implant survival.
5.The Clinical Utility of Biomarkers in Diagnosing Major Depressive Disorder in Adults: A Systematic Review of Literature From 2013 to 2023
Shi-han ANG ; Roger C. HO ; Roger S. MCINTYRE ; Zhisong ZHANG ; Soon-kiat CHANG ; Kayla M. TEOPIZ ; Cyrus SH HO
Psychiatry Investigation 2025;22(4):341-356
Objective:
The variety and efficacy of biomarkers available that may be used objectively to diagnose major depressive disorder (MDD) in adults are unclear. This systematic review aims to identify and evaluate the variety of objective markers used to diagnose MDD in adults.
Methods:
The search strategy was applied via PubMed and PsycINFO over the past 10 years (2013–2023) to capture the latest available evidence supporting the use of biomarkers to diagnose MDD. Data was reported through narrative synthesis.
Results:
Forty-two studies were included in the review. Findings were synthesised based on the following measures: blood, neuroimagingeurophysiology, urine, dermatological, auditory, vocal, cerebrospinal fluid and combinatory—and evaluated based on its sensitivity/specificity and area under the curve values. The best predictors of blood (MYT1 gene), neuroimagingeurophysiological (5-HT1A auto-receptor binding in the dorsal and median raphe), urinary (combined albumin, AMBP, HSPB, APOA1), cerebrospinal fluid-based (neuron specific enolase, microRNA) biomarkers were found to be closely linked to the pathophysiology of MDD.
Conclusion
A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.
6.Development of Zinc-Containing Chitosan/Gelatin Coatings with Immunomodulatory Effect for Soft Tissue Sealing around Dental Implants
Jing HAN ; Jorine G. F. SANDERS ; Lea ANDRÉE ; Bart A. J. A. van OIRSCHOT ; Adelina S. PLACHOKOVA ; Jeroen J. J. P. van den BEUCKEN ; Sander C. G. LEEUWENBURGH ; Fang YANG
Tissue Engineering and Regenerative Medicine 2025;22(1):57-75
BACKGROUND:
Soft tissue integration (STI) around dental implant abutments is a prerequisite to prevent bacterial invasion and achieve successful dental implant rehabilitation. However, peri-implant STI is a major challenge after dental abutment placement due to alterations in the immune microenvironment upon surgical dental implant installation.
METHODS:
Based on known immunomodulatory effects of zinc, we herein deposited zinc/chitosan/gelatin (Zn/CS/Gel) coatings onto titanium substrates to study their effect on macrophages. First, we exposed macrophages to cell culture media containing different zinc ion (Zn2+) concentrations. Next, we explored the immunomodulatory effect of Zn/CS/Gel coatings prepared via facile electrophoretic deposition (EPD).
RESULTS:
We found that Zn2+ effectively altered the secretome by reducing the secretion of pro-inflammatory and enhancing pro-regenerative cytokine secretion, particularly at a Zn2+ supplementation of approximately 37.5 μM. Zn/CS/Gel coatings released Zn2+ in a concentration range which effectively stimulated pro-regenerative macrophage polarization as demonstrated by M2 macrophage polarization. Additionally, the impact of these Zn2+-exposed macrophages on gingival fibroblasts incubated in conditioned medium showed stimulated adhesion, proliferation, and collagen secretion.
CONCLUSION
Our promising results suggest that controlled release of Zn2+ from Zn/CS/Gel coatings could be applied to immunomodulate peri-implant STI, and to enhance dental implant survival.
7.The Clinical Utility of Biomarkers in Diagnosing Major Depressive Disorder in Adults: A Systematic Review of Literature From 2013 to 2023
Shi-han ANG ; Roger C. HO ; Roger S. MCINTYRE ; Zhisong ZHANG ; Soon-kiat CHANG ; Kayla M. TEOPIZ ; Cyrus SH HO
Psychiatry Investigation 2025;22(4):341-356
Objective:
The variety and efficacy of biomarkers available that may be used objectively to diagnose major depressive disorder (MDD) in adults are unclear. This systematic review aims to identify and evaluate the variety of objective markers used to diagnose MDD in adults.
Methods:
The search strategy was applied via PubMed and PsycINFO over the past 10 years (2013–2023) to capture the latest available evidence supporting the use of biomarkers to diagnose MDD. Data was reported through narrative synthesis.
Results:
Forty-two studies were included in the review. Findings were synthesised based on the following measures: blood, neuroimagingeurophysiology, urine, dermatological, auditory, vocal, cerebrospinal fluid and combinatory—and evaluated based on its sensitivity/specificity and area under the curve values. The best predictors of blood (MYT1 gene), neuroimagingeurophysiological (5-HT1A auto-receptor binding in the dorsal and median raphe), urinary (combined albumin, AMBP, HSPB, APOA1), cerebrospinal fluid-based (neuron specific enolase, microRNA) biomarkers were found to be closely linked to the pathophysiology of MDD.
Conclusion
A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.
8.Development of Zinc-Containing Chitosan/Gelatin Coatings with Immunomodulatory Effect for Soft Tissue Sealing around Dental Implants
Jing HAN ; Jorine G. F. SANDERS ; Lea ANDRÉE ; Bart A. J. A. van OIRSCHOT ; Adelina S. PLACHOKOVA ; Jeroen J. J. P. van den BEUCKEN ; Sander C. G. LEEUWENBURGH ; Fang YANG
Tissue Engineering and Regenerative Medicine 2025;22(1):57-75
BACKGROUND:
Soft tissue integration (STI) around dental implant abutments is a prerequisite to prevent bacterial invasion and achieve successful dental implant rehabilitation. However, peri-implant STI is a major challenge after dental abutment placement due to alterations in the immune microenvironment upon surgical dental implant installation.
METHODS:
Based on known immunomodulatory effects of zinc, we herein deposited zinc/chitosan/gelatin (Zn/CS/Gel) coatings onto titanium substrates to study their effect on macrophages. First, we exposed macrophages to cell culture media containing different zinc ion (Zn2+) concentrations. Next, we explored the immunomodulatory effect of Zn/CS/Gel coatings prepared via facile electrophoretic deposition (EPD).
RESULTS:
We found that Zn2+ effectively altered the secretome by reducing the secretion of pro-inflammatory and enhancing pro-regenerative cytokine secretion, particularly at a Zn2+ supplementation of approximately 37.5 μM. Zn/CS/Gel coatings released Zn2+ in a concentration range which effectively stimulated pro-regenerative macrophage polarization as demonstrated by M2 macrophage polarization. Additionally, the impact of these Zn2+-exposed macrophages on gingival fibroblasts incubated in conditioned medium showed stimulated adhesion, proliferation, and collagen secretion.
CONCLUSION
Our promising results suggest that controlled release of Zn2+ from Zn/CS/Gel coatings could be applied to immunomodulate peri-implant STI, and to enhance dental implant survival.
9.The Clinical Utility of Biomarkers in Diagnosing Major Depressive Disorder in Adults: A Systematic Review of Literature From 2013 to 2023
Shi-han ANG ; Roger C. HO ; Roger S. MCINTYRE ; Zhisong ZHANG ; Soon-kiat CHANG ; Kayla M. TEOPIZ ; Cyrus SH HO
Psychiatry Investigation 2025;22(4):341-356
Objective:
The variety and efficacy of biomarkers available that may be used objectively to diagnose major depressive disorder (MDD) in adults are unclear. This systematic review aims to identify and evaluate the variety of objective markers used to diagnose MDD in adults.
Methods:
The search strategy was applied via PubMed and PsycINFO over the past 10 years (2013–2023) to capture the latest available evidence supporting the use of biomarkers to diagnose MDD. Data was reported through narrative synthesis.
Results:
Forty-two studies were included in the review. Findings were synthesised based on the following measures: blood, neuroimagingeurophysiology, urine, dermatological, auditory, vocal, cerebrospinal fluid and combinatory—and evaluated based on its sensitivity/specificity and area under the curve values. The best predictors of blood (MYT1 gene), neuroimagingeurophysiological (5-HT1A auto-receptor binding in the dorsal and median raphe), urinary (combined albumin, AMBP, HSPB, APOA1), cerebrospinal fluid-based (neuron specific enolase, microRNA) biomarkers were found to be closely linked to the pathophysiology of MDD.
Conclusion
A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.
10.Development of Zinc-Containing Chitosan/Gelatin Coatings with Immunomodulatory Effect for Soft Tissue Sealing around Dental Implants
Jing HAN ; Jorine G. F. SANDERS ; Lea ANDRÉE ; Bart A. J. A. van OIRSCHOT ; Adelina S. PLACHOKOVA ; Jeroen J. J. P. van den BEUCKEN ; Sander C. G. LEEUWENBURGH ; Fang YANG
Tissue Engineering and Regenerative Medicine 2025;22(1):57-75
BACKGROUND:
Soft tissue integration (STI) around dental implant abutments is a prerequisite to prevent bacterial invasion and achieve successful dental implant rehabilitation. However, peri-implant STI is a major challenge after dental abutment placement due to alterations in the immune microenvironment upon surgical dental implant installation.
METHODS:
Based on known immunomodulatory effects of zinc, we herein deposited zinc/chitosan/gelatin (Zn/CS/Gel) coatings onto titanium substrates to study their effect on macrophages. First, we exposed macrophages to cell culture media containing different zinc ion (Zn2+) concentrations. Next, we explored the immunomodulatory effect of Zn/CS/Gel coatings prepared via facile electrophoretic deposition (EPD).
RESULTS:
We found that Zn2+ effectively altered the secretome by reducing the secretion of pro-inflammatory and enhancing pro-regenerative cytokine secretion, particularly at a Zn2+ supplementation of approximately 37.5 μM. Zn/CS/Gel coatings released Zn2+ in a concentration range which effectively stimulated pro-regenerative macrophage polarization as demonstrated by M2 macrophage polarization. Additionally, the impact of these Zn2+-exposed macrophages on gingival fibroblasts incubated in conditioned medium showed stimulated adhesion, proliferation, and collagen secretion.
CONCLUSION
Our promising results suggest that controlled release of Zn2+ from Zn/CS/Gel coatings could be applied to immunomodulate peri-implant STI, and to enhance dental implant survival.

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